Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetics of Vasodilators

Part I

  • Review Article
  • Drug Disposition
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Understanding the mechanism of action and the pharmacokinetic properties of vasodilatory drugs facilitates optimal use in clinical practice. It should be kept in mind that a drug belongs to a class but is a distinct entity, sometimes derived from a prototype to achieve a specific effect. The most common pharmacokinetic drug improvement is the development of a drug with a half-life sufficiently long to allow an adequate once-daily dosage. Developing a controlled release preparation can increase the apparent half-life of a drug. Altering the molecular structure may also increase the half-life of a prototype drug. Another desirable improvement is increasing the specificity of a drug, which may result in fewer adverse effects, or more efficacy at the target site. This is especially important for vasodilatory drugs which may be administered over decades for the treatment of hypertension, which usually does not interfere with subjective well-being. Compliance is greatly increased with once-daily dosing.

Vasodilatory agents cause relaxation by either a decrease in cytoplasmic calcium, an increase in nitric oxide (NO) or by inhibiting myosin light chain kinase. They are divided into 9 classes: calcium antagonists, potassium channel openers, ACE inhibitors, angiotensin-II receptor antagonists, α-adrenergic and imidazole receptor antagonists, β1-adrenergic agonists, phosphodiesterase inhibitors, eicosanoids and NO donors.

Despite chemical differences, the pharmacokinetic properties of calcium antagonists are similar. Absorption from the gastrointestinal tract is high, with all substances undergoing considerable first-pass metabolism by the liver, resulting in low bioavailability and pronounced individual variation in pharmacokinetics. Renal impairment has little effect on pharmacokinetics since renal elimination of these agents is minimal. Except for the newer drugs of the dihydropyridine type, amlodipine, felodipine, isradipine, nilvadipine, nisoldipine and nitrendipine, the half-life of calcium antagonists is short. Maintaining an effective drug concentration for the remainder of these agents requires multiple daily dosing, in some cases even with controlled release formulations. However, a coat-core preparation of nifedipine has been developed to allow once-daily administration. Adverse effects are directly correlated to the potency of the individual calcium antagonist.

Treatment with the potassium channel opener minoxidil is reserved for patients with moderately severe to severe hypertension which is refractory to other treatment. Diazoxide and hydralazine are chiefly used to treat severe hypertensive emergencies, primary pulmonary and malignant hypertension and in severe pre-eclampsia.

ACE inhibitors prevent conversion of angiotensin-I to angiotensin-II and are most effective when renin production is increased. Since ACE is identical to kininase-II, which inactivates the potent endogenous vasodilator bradykinin, ACE inhibition causes a reduction in bradykinin degradation. ACE inhibitors exert cardioprotective and cardioreparative effects by preventing and reversing cardiac fibrosis and ventricular hypertrophy in animal models. The predominant elimination pathway of most ACE inhibitors is via renal excretion. Therefore, renal impairment is associated with reduced elimination and a dosage reduction of 25 to 50% is recommended in patients with moderate to severe renal impairment.

Separating angiotensin-II inhibition from bradykinin potentiation has been the goal in developing angiotensin-II receptor antagonists. The incidence of adverse effects of such an agent, losartan, is comparable to that encountered with placebo treatment, and the troublesome cough associated with ACE inhibitors is absent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ruth P, Wang GX, Boekhoff I, et al. Transfected cGMP-dependent protein kinase suppresses calcium transients by inhibition of inositol 1,4,5-triphosphate production. Proc Natl Acad Sci U S A 1993; 90: 2623–7.

    Article  PubMed  CAS  Google Scholar 

  2. Walsh MP, Kargacin GJ, Kendrick-Jones J, et al. Intracellular mechanisms involved in the regulation of vascular smooth muscle tone. Can J Physiol Pharmacol 1995; 73: 565–73.

    Article  PubMed  CAS  Google Scholar 

  3. Lincoln TM, Komalavilas P, Cornwell TL. Pleiotropic regulation of vascular smooth muscle tone by cyclic GMP-dependent protein kinase. Hypertension 1994; 23: 1141–7.

    Article  PubMed  CAS  Google Scholar 

  4. Rembold CM. Regulation of contraction and relaxation in arterial smooth muscle. Hypertension 1992; 20: 129–37.

    Article  PubMed  CAS  Google Scholar 

  5. Shah AM, Mebazaa A, Wetzel RC, et al. Novel cardiac myofilament desensitizing factor released by endocardial and vascular endothelial cells. Circulation 1994; 89: 2492–7.

    Article  PubMed  CAS  Google Scholar 

  6. Bode-Böger SM, Böger RH, Alfke H, et al. L-arginine induces nitric oxide-dependent vasodilationin patients with critical limb ischemia. Circulation 1996; 93: 85–90.

    Article  PubMed  Google Scholar 

  7. Rang HP, Dale MM, Ritter JM. The circulation. In: Pharmacology. Edinburgh: Churchill Livingstone, 1995: 301–22.

    Google Scholar 

  8. Scholz H. Calcium-Antagonisten. In: Schwabe U, Pfaffrath D, editors. Arzneiverordnungs-Report 95. Stuttgart: Gustav Fischer Verlag, 1995: 166–73.

    Google Scholar 

  9. Benet LZ, Oie S, Schwartz JB. Design and optimization of dosage regimens: pharmacokinetic data. In: Hardman JG, Limbird LE, Molinoff PB, et al., editors. The pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996: 1707–92.

    Google Scholar 

  10. Vaghy P. Calcium antagonists. In: Brody TM, Larner J, Minneman KP, et al., editors. Human pharmacology. St Louis: Mosby, 1994: 203–13.

    Google Scholar 

  11. Tam YK. Individual variation in first-pass metabolism. Clin Pharmacokinet 1993; 25: 300–28.

    Article  PubMed  CAS  Google Scholar 

  12. Kelly JG, O’Malley K. Clinical pharmacokinetics of calcium antagonists. Clin Pharmacokinet 1992; 22: 416–33.

    Article  PubMed  CAS  Google Scholar 

  13. Swan SK, Bennett WM. Drug dosing guidelines in patients with renal failure. West J Med 1992; 156: 633–8.

    PubMed  CAS  Google Scholar 

  14. Echizen H, Eichelbaum M. Clinical pharmacokinetics of verapamil, nifedipine and diltiazem. Clin Pharmacokinet 1986; 11: 425–49.

    Article  PubMed  CAS  Google Scholar 

  15. Tokuma Y, Noguchi H. Stereoselective pharmacokinetics of dihydropyridine calcium antagonists. J Chromatogr 1995; 694: 181–94.

    Article  CAS  Google Scholar 

  16. Schwartz JB, Troconiz IF, Verotta D, et al. Aging effects on stereoselective pharmacokinetics and pharmacodynamics of verapamil. J Pharmacol Exp Ther 1993; 265: 690–8.

    PubMed  CAS  Google Scholar 

  17. Hunt BA, Self TH, Lalonde RL, et al. Calcium channel blockers as inhibitors of drug metabolism. Chest 1989; 96: 393–9.

    Article  PubMed  CAS  Google Scholar 

  18. Schall R, Müller FR, Müller FO, et al. Bioequivalence of controlled release calcium antagonists. Clin Pharmacokinet 1997; 32: 75–89.

    Article  PubMed  CAS  Google Scholar 

  19. Pahor M, Manto A, Pedone C, et al. Age and severe adverse drug reactions caused by nifedipine and verapamil. J Clin Epidemiol 1996; 49: 921–8.

    Article  PubMed  CAS  Google Scholar 

  20. Chellingsworth MC, Kendall MJ, Wright AD, et al. The effects of verapamil, diltiazem, nifedipine and propranolol on metabolic control in hypertensives with non-insulin dependent diabetes mellitus. J Hum Hypertens 1989; 3: 35–9.

    PubMed  CAS  Google Scholar 

  21. Dilmen U, Cagler MK, Senses A, et al. Nifedipine in hypertensive emergencies of children. Am J Dis Child 1983; 137: 1162–5.

    PubMed  CAS  Google Scholar 

  22. Roth B, Herkenrath P, Krebber J, et al. Nifedipine in hypertensive crises of infants and children. Clin Exp Hypertens 1986; A8: 871–7.

    Article  Google Scholar 

  23. Lopez-Herce J, Albajara L, Cagigas P, et al. Treatment of hypertensive crisis in children with nifedipine. Intensive Care Med 1988; 14: 519–21.

    Article  PubMed  CAS  Google Scholar 

  24. Kallenberg CG, Wouda AA, Kuitert JJ, et al. Nifedipine in Raynauds phenomenon: relationship between immediate, shortterm and long-term effects. J Rheumatol 1987; 14: 284–90.

    PubMed  CAS  Google Scholar 

  25. Dickinson DF, Wilson N, Curry P. Use of nifedipine in hypertrophic cardiomyopathy in infants: a report of two cases. Int J Cardiol 1985; 7: 159–60.

    Article  PubMed  CAS  Google Scholar 

  26. Beer N, Gallegos I, Cohen A, et al. Efficacy of sublingual nifedipine in the acute treatment of systemic hypertension. Chest 1981; 79: 571–4.

    Article  PubMed  CAS  Google Scholar 

  27. Foster TS, Hamann SR, Richards VR, et al. Nifedipine kinetics and bioavailability after single intravenous and oral doses in normal subjects. J Clin Pharmacol 1983; 23: 161–70.

    PubMed  CAS  Google Scholar 

  28. Kleinbloesem CH, Van Brummelen P, Van de Linde JA, et al. Nifedipine: kinetics and dynamics in healthy subjects. Clin Pharmacol Ther 1984; 35: 742–9.

    Article  PubMed  CAS  Google Scholar 

  29. Soons PA, Schoemaker HC, Cohen AF, et al. Intraindividual variability in nifedipine pharmacokinetics and effects in healthy subjects. J Clin Pharmacol 1992; 32: 324–31.

    PubMed  CAS  Google Scholar 

  30. Speight TM, Holford NHG, editors. Avery’s drug treatment. 4th ed. Auckland: Adis International, 1997.

    Google Scholar 

  31. Van Bortel L, Bohm R, Mooij J, et al. Total and free steady-state plasma levels and pharmacokinetics of nifedipine in patients with terminal renal failure. Eur J Clin Pharmacol 1989; 37: 185–9.

    Article  PubMed  Google Scholar 

  32. Odar-Cederlof I, Anderson P, Bondesson U. Nifedipine as an antihypertensive drug in patients with renal failure: pharmacokinetics and effects. J Intern Med 1990; 227: 329–37.

    Article  PubMed  CAS  Google Scholar 

  33. Bennett WM, Aronoff GR, Golper TA, et al. Drug prescribing in renal failure. Philadelphia: American College of Physicians, 1987.

    Google Scholar 

  34. Ene MD, Roberts CJ. Pharmacokinetics of nifedipine after oral administration in chronic liver disease. J Clin Pharmacol 1987; 27: 1001–4.

    PubMed  CAS  Google Scholar 

  35. Visser W, Wallenburg HC. A comparison between the haemodynamic effects of oral nifedipine and intravenous dihydralazine in patients with severe pre-eclampsia. J Hypertens 1995; 13: 791–5.

    Article  PubMed  CAS  Google Scholar 

  36. Prevost RR, Akl SA, Whybrew WD, et al. Oral nifedipine pharmacokinetics in pregnancy-induced hypertension. Pharmacotherapy 1992; 12: 174–7.

    PubMed  CAS  Google Scholar 

  37. Manninen A. Nifedipine reduces thromboxane A2 production by platelets without changing aggregation in hypertensive pregnancy. Pharmacol Toxicol 1996; 78: 387–91.

    Article  PubMed  CAS  Google Scholar 

  38. Bennett PN. Drugs in human lactation. Amsterdam: Elsevier, 1988.

    Google Scholar 

  39. Robertson DR, Waller DG, Renwick AG, et al. Age-related changes in the pharmacokinetics and pharmacodynamics of nifedipine. Br J Clin Pharmacol 1988; 25: 297–305.

    Article  PubMed  CAS  Google Scholar 

  40. Scott M, Castleden CM, Adam HK, et al. The effect of ageing on the dispostion of nifedipine and atenolol. Br J Clin Pharmacol 1988; 25: 289–96.

    Article  PubMed  CAS  Google Scholar 

  41. Saseen JJ, Carter BL, Brown TER, et al. Comparison of nifedipine alone and with diltiazem or verapamil in hypertension. Hypertens 1996; 28: 109–14.

    Article  CAS  Google Scholar 

  42. Kirch W, Kleinbloesem CH, Belz GG. Drug interactions with calcium antagonists. Pharmacol Ther 1990; 45: 109–36.

    Article  PubMed  CAS  Google Scholar 

  43. Lessem JN. Interaction between Ca2+ antagonists and digitalis. Cardiovasc Drugs Ther 1988; 1: 441–6.

    Article  PubMed  CAS  Google Scholar 

  44. Klein MD, Weiner DA. Antianginal and antihypertensive properties of slow release verapamil. In: Fleckenstein A, editor. Hypertension — the next decade: verapamil in focus. Edinburgh: Churchill Livingstone, 1987: 154–60.

    Google Scholar 

  45. Kirsten E, Guerrero J, Müller-Peltzer H. Pharmacokinetics of a slow release formulation. In: Fleckenstein A, editor. Hypertension — the next decade: verapamil in focus. Edinburgh: Churchill Livingstone, 1987: 274–9.

    Google Scholar 

  46. Abernethy DR, Schwartz JB. Verapamil pharmacodynamics and disposition in obese hypertensive patients. J Cardiovasc Pharmacol 1988; 11: 209–15.

    PubMed  CAS  Google Scholar 

  47. Opie LH. Calcium channel antagonists. VI: clinical pharmacokinetics of first and second-generation agents. Cardiovasc Drugs Ther 1989; 3: 482–97.

    Article  PubMed  CAS  Google Scholar 

  48. Frishman WH, Kirsten E, Klein M. Clinical relevance of verapamil plasma levels in stable angina pectoris. Am J Cardiol 1982; 50: 1080–4.

    Google Scholar 

  49. Jr McAllister RG, Kirsten E. The pharmacology of verapamil. IV: kinetic and dynamic effects after single intravenous and oral doses. Clin Pharmacol Ther 1982; 31: 418–26.

    Article  PubMed  CAS  Google Scholar 

  50. McTavish D, Sorkin EM. Verapamil: an updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in hypertension. Drugs 1989; 38: 19–76.

    Article  PubMed  CAS  Google Scholar 

  51. Freedman SB, Richmond DR, Ashley JJ, et al. Verapamil kinetics in normal subjects and patients with coronary artery spasm. Clin Pharmacol Ther 1981; 30: 644–52.

    Article  PubMed  CAS  Google Scholar 

  52. Jespersen CM, Frederiksen M, Fischer Hansen J, et al. Orcadian variation in the pharmacokinetics of verapamil. Eur J Clin Pharmacol 1989; 37: 613–5.

    PubMed  CAS  Google Scholar 

  53. Gupta SK, Yih BM, Atkinson L, et al. The effect of food, time of dosing, and body position on the pharmacokinetics and pharmacodynamics of verapamil and norverapamil. J Clin Pharmacol 1995; 35: 1083–93.

    PubMed  CAS  Google Scholar 

  54. Tsang YCh, Pop R, Gordon P, et al. High variability in drug pharmacokinetics complicates determination of bioequivalence: experience with verapamil. Pharm Res 1996; 13: 846–50.

    Article  PubMed  CAS  Google Scholar 

  55. Mooy JM, Shols M, van Baak M, et al. Pharmacokinetics of verapamil in patients with renal failure. Eur J Clin Pharmacol 1985; 28: 405–11.

    Article  PubMed  CAS  Google Scholar 

  56. Rahn KH, van Bortel LM, Mooy JM. The use of calcium antagonists in patients with renal failure. J Hypertens 1987; 5 Suppl. 4: 67–9.

    Article  Google Scholar 

  57. Finucci GF, Padrini R, Piovan D, et al. Verapamil pharmacokinetics and liver function in patients with cirrhosis. Int J Clin Pharmacol Res 1988; VIII: 123–6.

    Google Scholar 

  58. McInnes GT. Clinical pharmacology of verapamil. Br J Clin Pract 1988; 42: 3–8.

    Google Scholar 

  59. Belfort M, Akovic K, Anthony J, et al. The effect of acute volume expansion and vasodilatation with verapamil on uterine and umbilical artery Doppler indices in severe preeclampsia. J Clin Ultrasound 1994; 22: 317–25.

    Article  PubMed  CAS  Google Scholar 

  60. Engelhardt W, Grabitz RG, Funk A, et al. Intrauterine therapy of fetal supraventricular tachycardia with digoxin and verapamil. Z Geburtshilfe Perinatal 1993; 197: 99–103.

    CAS  Google Scholar 

  61. Lechner W. Calcium antagonists in pregnancy as an antihypertensive and tocolytic agent. Wien Med Wochenschr 1993; 143: 519–21.

    PubMed  CAS  Google Scholar 

  62. Carosella L, Menichelli P, Alimenti M, et al. Verapamil disposition and cardiovascular effects in elderly patients after single intravenous and oral doses. Cardiovasc Drugs Ther 1989; 3: 417–25.

    Article  PubMed  CAS  Google Scholar 

  63. Storstein L, Larsen A, Midtbo K, et al. Pharmacokinetics of calcium blockers in patients with renal insufficiency and in geriatric patients. Acta Med Scand 1984; 681 Suppl.: 25–30.

    Google Scholar 

  64. Gupta SK, Atkinson L, Tu T, et al. Age and gender related changes in stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil. Br J Clin Pharmacol 1995; 40: 325–31.

    Article  PubMed  CAS  Google Scholar 

  65. Schwartz JB. Aging alters verapamil elimination and dynamics: single dose and steady-state responses. J Pharmacol Exp Ther 1990; 255: 364–73.

    PubMed  CAS  Google Scholar 

  66. Piepho RW, Culbertson VL, Rhodes RS. Drug interactions with the calcium-entry blockers. Circulation 1984; 75 Suppl. V: 181–94.

    Google Scholar 

  67. Lander R. Verapamil/beta-blocker interaction: a review. Mod Med 1983; 80: 626–9.

    CAS  Google Scholar 

  68. Schlanz KD, Myre SA, Bottorff MB. Pharmacokinetic interactions with calcium channel antagonists: Pt I. Clin Pharm 1991; 21: 344–56.

    Article  CAS  Google Scholar 

  69. Schulte-Sasse U, Tarnow J. Effects of short-term infusion of nifedipine or verapamil on systemic hemodynamics and left ventricular myocardial contractility in patients prior to coronary artery bypass surgery. Anesthesiology 1987; 67: 492–7.

    Article  PubMed  CAS  Google Scholar 

  70. Mclnnes GT, Thomson GD, Murray GD, et al. Intravenous verapamil during β-adrenoceptor blockade with propranolol [abstract]. Br J Clin Pharmacol 1986; 21: 580P.

    Google Scholar 

  71. Baeyens JM, Del Pozo E. Interactions between calcium channel blockers and non-cardiovascular drugs: interactions with drugs acting at the neuromuscular or the CNS level. Pharmacol Toxicol 1988; 62: 59–63.

    Article  PubMed  CAS  Google Scholar 

  72. Gordon M, Goldenberg LMC. Clinical digoxin toxicity in the aged in association with co-administered verapamil: a report of two cases and review of the literature. J Am Geriatr Soc 1986; 34: 659–62.

    PubMed  CAS  Google Scholar 

  73. Maggio TG, Bartels DW. Increased cyclosporine blood concentrations due to verapamil administration. Drug Intell Clin Pharm 1988; 22: 705–7.

    PubMed  CAS  Google Scholar 

  74. Stringer KA, Mallet J, Clarke M, et al. The effect of three different oral doses of verapamil on the disposition of theophylline. Eur J Clin Pharmacol 1992; 43: 35–8.

    Article  PubMed  CAS  Google Scholar 

  75. Bauer LA, Horn JR, Pettit H. Mixed-effect modeling for detection and evaluation of drug interactions: digoxin-quinidine and digoxin-verapamil combinations. Ther Drug Monit 1996; 18: 46–52.

    Article  PubMed  CAS  Google Scholar 

  76. Macphee GJA, McInnes GT, Thompson GG, et al. Verapamil potentiates carbamazepine neurotoxicity: a clinically important inhibitory interaction. Lancet 1986; I: 700–3.

    Article  Google Scholar 

  77. Trohman RG, Estes DM, Castellanos A, et al. Increased quinidine plasma concentrations during administration of verapamil: a new quinidine-verapamil interaction. Am J Cardiol 1986; 57: 706–7.

    Article  PubMed  CAS  Google Scholar 

  78. Mooy J, Bohm R, van Baak M, et al. The influence of antituberculosis drugs on the plasma level of verapamil. Eur J Clin Pharmacol 1987; 32: 107–9.

    Article  PubMed  CAS  Google Scholar 

  79. Fromm MF, Busse D, Kroemer HK, et al. Differential induction of prehepatic and hepatic metabolism of verapamil by rifampicin. Hepatology 1996; 24: 796–801.

    Article  PubMed  CAS  Google Scholar 

  80. Wright BA, Jarrett DB. Lithium and calcium channel blockers: possible neurotoxicity. Biol Psychiatry 1991; 30: 635–6.

    Article  PubMed  CAS  Google Scholar 

  81. Mikus G, Kroemer HK, Klotz U, et al. The effect of cimetidine on verapamil metabolism and renal excretion of metabolites. Clin Pharmacol Ther 1988; 43: 134.

    Google Scholar 

  82. Elliott HL, Meredith PA, Campbell L, et al. The combination of prazosin and verapamil in the treatment of hypertension. Clin Pharmacol Ther 1988; 43: 554–60.

    Article  PubMed  CAS  Google Scholar 

  83. Nalbantgil I, Onder R, Kiliccioglu B, et al. Verapamil and nitrendipine combination in the treatment of hypertension. Eur Heart J 1989; 10 Suppl.: 118.

    Google Scholar 

  84. Holzgreve H, Distler A, Michaelis J, et al. Verapamil versus hydrochlorothiazide in the treatment of hypertension: results of long-term double-blind comparative trial. BMJ 1989; 299: 881–6.

    Article  PubMed  CAS  Google Scholar 

  85. Stieren B, Bühler V, Hege HG, et al. Pharmacokinetics and metabolism of gallopamil. In: Kaltenbach M, Hopf R, editors. Gallopamil: pharmacological and clinical profile of a calcium antagonist. Berlin: Springer Verlag, 1984: 88–93.

    Google Scholar 

  86. Eichelbaum M. Pharmakokinetik und metabolismus von gallopamil. Z Kardiol 1989; 78 Suppl. 5: 20–4.

    Google Scholar 

  87. Brogden RN, Benfield P. Gallopamil: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in ischaemic hert disease. Drugs 1994; 47: 93–115.

    Article  PubMed  CAS  Google Scholar 

  88. Ishihara M, Sato H, Tateishi H, et al. Effects of various doses of intracoronary diltiazem on coronary resistance vessels in humans. Jpn Circ J 1995; 59: 790–8.

    Article  PubMed  CAS  Google Scholar 

  89. Bianchetti G, Billy S, Ascalone V, et al. Multicenter studies on the pharmacokinetic profile of sustained-release oral diltiazem (300mg) after once a day repeated administration: influence of age. Int J Clin Pharmacol Ther 1996; 34: 195–201.

    PubMed  CAS  Google Scholar 

  90. Chaffman M, Brogden RN. Diltiazem: a review of its pharmacological properties and therapeutic efficacy. Drugs 1985; 29: 387–454.

    Article  PubMed  CAS  Google Scholar 

  91. Morselli PL, Rovei V, Mitchard M, et al. Pharmacokinetics and metabolism of diltiazem in man (observations on healthy volunteers and angina pectoris patients). In: Bing RJ, editor. New drug therapy with a calcium antagonist. Amsterdam: Excerpta Medica 1979: 152–68.

    Google Scholar 

  92. Smith MS, Verghese CP, Shand DG, et al. Pharmacokinetic and pharmacodynamic effects of diltiazem. Am J Cardiol 1983; 51: 1369–74.

    Article  PubMed  CAS  Google Scholar 

  93. Dias VC, Weir SJ, Ellenbogen KA. Pharmacokinetics and pharmacodynamics of intravenous diltiazem in patients with atrial flatter or atrial flutter. Circulation 1992; 86: 1421–8.

    Article  PubMed  CAS  Google Scholar 

  94. Pozet N, Brazier JL, Hadj Aissa A, et al. Pharmacokinetics of diltiazem in severe renal failure. Eur J Clin Pharmacol 1983; 24: 635–8.

    Article  PubMed  CAS  Google Scholar 

  95. Grech-Belanger O, Langlois S, LeBoeuf E. Pharmacokinetics of diltiazem in patients undergoing continuous ambulatory peritoneal dialysis. J Clin Pharmacol 1988; 28: 477–80.

    PubMed  CAS  Google Scholar 

  96. Tawashi M, Marc-Aurèle J, Bichet D, et al. Pharmacokinetics of oral diltiazem and five of its metabolites in patients with chronic renal failure. Biopharm Drug Dispos 1991; 12: 95–104.

    Article  PubMed  CAS  Google Scholar 

  97. Rossini D, Falsini G, Palmerini L, et al. Overdosing on diltiazem in hepatic insufficiency. Clin Ther 1995; 146: 319–21.

    CAS  Google Scholar 

  98. Kurosawa S, Kurosawa N, Owada E, et al. Pharmacokinetics of diltiazem in patients with liver cirrhosis. Int J Clin Pharmacol Res 1990; 10: 311–8.

    PubMed  CAS  Google Scholar 

  99. Houde C, Bohn DJ, Freedom RM, et al. Profile of paediatric patients with pulmonary hypertension judged by responsiveness to vasodilators. Br Heart J 1993; 70: 461–8.

    Article  PubMed  CAS  Google Scholar 

  100. Smith CL, Hampton EM, Pederson JA, et al. Clinical and medicoeconomic impact of the cyclosporine-diltiazem interaction in renal transplant recipients. Pharmacotherapy 1994; 14: 471–81.

    PubMed  CAS  Google Scholar 

  101. Gotze S, Auch-Schwelk W, Bossaller C, et al. Preventive effects of diltiazem on cyclosporin A-induced vascular smooth muscle dysfunction. Transpl Int 1994; 7: 157–62.

    Article  PubMed  CAS  Google Scholar 

  102. Rutsch W, Schmutzler H. Comparison of the acute hemodynamic effects of nifedipine with nitrendipine and a study of the electrophysiological effects of nitrendipine in man. J Cardiovasc Pharmacol 1984; 6: S1011–5.

    Article  PubMed  Google Scholar 

  103. Maltz MB, Davies DW, Lau CP, et al. The effects of oral nitrendipine and propranolol, alone and in combination, on hypertensive patients with special reference to AV conduction. Br J Clin Pharmacol 1986; 22: 463–7.

    Article  PubMed  CAS  Google Scholar 

  104. Goa KL, Sorkin EM. Nitrendipine: a review of pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of hypertension. Drugs 1987; 33: 123–55.

    Article  PubMed  CAS  Google Scholar 

  105. Esper RJ, Machado RA, Esper RC, et al. Dose assessment and long-term effectiveness of nitrendipine in the treatment of mild and moderate hypertensive patients. J Cardiovasc Pharmacol 1987; 9 Suppl. 4: 164–8.

    Article  Google Scholar 

  106. Kann J, Krol GJ, Raemsch KD, et al. Bioequivalence and metabolism of nitrendipine administered orally to healthy volunteers. J Cardiovasc Pharmacol 1984; 6: S968–73.

    Article  PubMed  CAS  Google Scholar 

  107. Soons PA, Breimer DD. Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy male subjects. Br J Clin Pharmacol 1991; 32: 11–6.

    Article  PubMed  CAS  Google Scholar 

  108. Aronoff GR, Sloan RS. Nitrendipine kinetics in normal and impaired renal function. Clin Parmacol Ther 1985; 38: 212–8.

    Article  CAS  Google Scholar 

  109. Soons PA, Ankermann T, Breimer DD, et al. Stereoselective pharmacokinetics of oral nitrendipine in elderly hypertensive patients with normal and impaired renal function. Eur J Clin Pharmacol 1992; 42: 423–7.

    Article  PubMed  CAS  Google Scholar 

  110. Van Bortel L, Bohm R, Mooy J, et al. Pharmacokinetics of nitrendipine in terminal renal failure. Eur J Clin Pharmacol 1989; 36: 467–71.

    Article  PubMed  Google Scholar 

  111. Mikus G, Fischer C, Heuer B, et al. Application of stable isotope methodology to study the pharmacokinetics, bioavailability and metabolism of nitrendipine after i.v and p.o. administration. Br J Clin Pharmacol 1987; 24: 561–9.

    Article  PubMed  CAS  Google Scholar 

  112. Kierdorf H, Müller A, Blanke PM, et al. Pharmacodynamics and pharmacokinetics of oral nitrendipine solution in hypertensive patients with advanced renal failure. Eur J Clin Pharmacol 1993; 45: 129–34.

    Article  PubMed  CAS  Google Scholar 

  113. Lasseter KC, Shamblen EC, Murdoch AA, et al. Steady state pharmacokinetics of nitrendipine in hepatic insufficiency. J Cardiovasc Pharmacol 1984; 6: S977–81.

    Article  PubMed  CAS  Google Scholar 

  114. Eichelbaum M, Mikus G, Mast V, et al. Pharmacokinetics and pharmacodynamics of nitrendipine in healthy subjects and patients with kidney and liver disease. J Cardiovasc Pharmacol 1988; 12 Suppl. 4: S6–10.

    Article  Google Scholar 

  115. Kiowski W, Bühler FR, Fadayomi MO, et al. Age, race, blood pressure and renin: predictors for antihypertensive treatment with calcium antagonists. Am J Cardiol 1985; 56: 81H–5H.

    Article  PubMed  CAS  Google Scholar 

  116. Wells TG, Sinaiko AR. Antihypertensive effect and pharmacokinetics of nitrendipine in children. J Pediatr 1991; 118: 638–43.

    Article  PubMed  CAS  Google Scholar 

  117. Kendall MJ, Lobo J, Jack DB, et al. The influence of age on the pharmacokinetics of nitrendipine. J Cardiovasc Pharmacol 1987; 9: S96–100.

    Article  Google Scholar 

  118. Lettieri JT, Krol GJ, Yeh SC, et al. The effects of age and race on nitrendipine pharmacokinetics and pharmacodynamics. J Cardiovasc Pharmacol 1988; 12 Suppl. 4: S129–32.

    Article  Google Scholar 

  119. Moser M, Lunn J, Nash DT, et al. Nitrendipine in the treatment of mild to moderate hypertension. J Cardiovasc Pharmacol 1984; 6: S1085–9.

    Article  PubMed  Google Scholar 

  120. Ljung B. Vascular selectivity of felodipine. Drugs 1985; 29 Suppl. 2: 46–58.

    Article  Google Scholar 

  121. Edgar B, Collste P, Haglund K, et al. Pharmacokinetic and haemodynamic effects of felodipine as monotherapy in hypertensive patients. Clin Invest Med 1987; 10: 388–94.

    PubMed  CAS  Google Scholar 

  122. Rönn O, Bengtsson B, Edgar B, et al. Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol. Drugs 1985; 29 Suppl. 2: 16–25.

    Article  Google Scholar 

  123. Amlie JP, Endresen K, Sire S. The effect of felodipine on the sinus and atrioventricular nodes in patients with ischemic heart disease. J Cardiovasc Pharmacol 1990; 15 Suppl. 4: 25.

    Article  Google Scholar 

  124. Little WC, Cheng CP. Vascular versus myocardial effects of calcium antagonists. Drugs 1994; 47 Suppl. 4: 41–5.

    Article  Google Scholar 

  125. Achilli F, Buono G, Di Fraia S, et al. Acute and chronic effects of felodipine extended release and amlodipine in patients with exertional angina: a double-masked, clinical comparison. Curr Ther Res 1996; 57: 523–36.

    Article  CAS  Google Scholar 

  126. Emanuelsson H, Ekström L, Hjalmarson A, et al. Felodipineinduced dilatation of epicardial coronary arteris: a randomized, double blind study. Angiology 1986; 37: 1–7.

    Article  PubMed  CAS  Google Scholar 

  127. Leonetti G, Gradnik R, Terzoli L, et al. Effects of single and repeated doses of the calcium antagonist felodipine on blood pressure renal function, electrolytes and water bilance and renin angiotensin-aldosterone system in hypertensive patients. J Cardiovasc Pharmacol 1986; 8: 1243–8.

    Article  PubMed  CAS  Google Scholar 

  128. Dunselman PHJM, Edgar B. Felodipine clinical pharmacokinetics. Clin Pharmacokinet 1991; 21: 418–30.

    Article  PubMed  CAS  Google Scholar 

  129. Edgar B, Lundborg P, Regårdh CG. Clinical pharmacokinetics of felodipine. Drugs 1987; 34 Suppl. 3: 16–27.

    Article  Google Scholar 

  130. Blychert E. Felodipine pharmacokinetics and plasma concentration vs effect relationship. Blood Press 1992; 2 Suppl.: 1–30.

    Google Scholar 

  131. Edgar B, Regårdh CG, Johnsson G, et al. Felodipine kinetics in healthy men. Clin Pharmacol Ther 1985; 38: 205–11.

    Article  PubMed  CAS  Google Scholar 

  132. Edgar B, Hoffman KS, Lundborg P, et al. Absorption, distribution and elimination of felodipine in man. Drugs 1985; 29 Suppl. 2: 9–15.

    Article  Google Scholar 

  133. Edgar B, Regardh CG, Attman PO, et al. Pharmacokinetics of felodipine in patients with impaired renal function. Br J Clin Pharmacol 1989; 27: 67–74.

    Article  PubMed  CAS  Google Scholar 

  134. Larsson R, Karlberg BE, Gelin A, et al. Acute and steady-state pharmacokinetics and antihypertensive effects of felodipine in patients with normal and impaired renal function. J Clin Pharmacol 1990; 30: 1020–30.

    PubMed  CAS  Google Scholar 

  135. Danielsson BR, Reiland S, Rundqvist E, et al. Digital defects induced by vasodilating agents: relationship to reduction in uteroplacental blood flow. Teratology 1989; 40: 351–8.

    Article  PubMed  CAS  Google Scholar 

  136. Blowey DL, Moncica L, Scolnik D, et al. The pharmacokinetics of extended release felodipine in children. Eur J Clin Pharmacol 1996; 50: 147–8.

    Article  PubMed  CAS  Google Scholar 

  137. Wade JR, Sambol NC. Felodipine population dose-response and concentration-response relationships in patients with essential hypertension. Clin Pharmacol Ther 1995; 57: 569–81.

    Article  PubMed  CAS  Google Scholar 

  138. Blychert E, Edgar B, Elmfeldt D, et al. A population study of the pharmacokinetics of felodipine. Br J Clin Pharmacol 1991; 31: 15–24.

    Article  PubMed  CAS  Google Scholar 

  139. Van der Krogt JP, Brand R, Dawson EC. Amlodipine versus extended-release felodipine in general practice: a randomized, parallel-group study in patients with mild-to-moderate hypertension. Curr Ther Res 1996; 57: 145–58.

    Article  Google Scholar 

  140. Carruthers SG, Bailey DG. Tolerance and cardiovascular effects of single dose felodipine/β-blocker combinations in healthy subjects. J Cardiovasc Pharmacol 1987; 10 Suppl. 1: 169–77.

    Article  Google Scholar 

  141. Pedersen EB, Sorensen SS, Eiskjaer H, et al. Interaction between cyclosporine and felodipine in renal transplant patients. Kidney Int 1992; 36 Suppl.: 82–6.

    Google Scholar 

  142. Sorensen SS, Skoubon H, Eiskjaer H, et al. Effect of felodipine on renal hemodynamics and tubular sodium handling in cyclosporine-treated renal transplant recipients. Nephrol Dial Transplant 1992; 7: 69–78.

    PubMed  CAS  Google Scholar 

  143. Madsen JK, Jensen JD, Jensen LW, et al. Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine. Eur J Clin Pharmacol 1996; 50: 203–8.

    Article  PubMed  CAS  Google Scholar 

  144. Langley MS, Sorkin EM. Nimodipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cerebrovascular disease. Drugs 1989; 37: 669–99.

    Article  PubMed  CAS  Google Scholar 

  145. Mück W, Breuekl HP, Kuhlmann J. The influence of age on the pharmacokinetics of nimodipine. Int J Clin Pharmacol Ther Toxicol 1996; 34: 293–8.

    Google Scholar 

  146. Wagenknecht LE, Furberg CD, Hammon JW, et al. Surgical bleeding: unexpected effects of a calcium antagonist. BMJ 1995; 310: 776–7.

    Article  PubMed  CAS  Google Scholar 

  147. Faulkner JK, McGibney D, Chasseaud LF, et al. The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol 1986; 22: 21–5.

    Article  PubMed  CAS  Google Scholar 

  148. Meredith PA, Elliott HL. Clinical pharmacokinetics of amlodipine. Clin Pharmacokinet 1992; 22: 22–31.

    Article  PubMed  CAS  Google Scholar 

  149. Opie LH. Clinical use of calcium channel antagonist drugs. 2nd ed. Boston: Kluwer Academic Publishers, 1990.

    Google Scholar 

  150. Elliott HL, Meredith PA, Reid JL, et al. A comparison of the disposition of single oral doses of amlodipine in young and elderly subjects. J Cardiovasc Pharmacol 1988; 12 Suppl. 7: S64–6.

    Article  Google Scholar 

  151. Van Zwieten PA, Pfaffendorf M. Similarities and differences between calcium antagonists: pharmacological aspects. J Hypertens 1993; 11 Suppl. 1: S3–11.

    Article  Google Scholar 

  152. Taylor SH. Usefulness of amlodipine for angina pectoris. Am J Cardiol 1994; 73: 28A–33A.

    Article  PubMed  CAS  Google Scholar 

  153. Lehmann G, Reiniger G, Beyerle A, et al. Pharmacokinetics and additional anti-ischaemic effectiveness of amlodipine, a once-daily calcium antagonist during acute and long-term therapy of stable angina pectoris in patients pretreated with a betablocker. Eur Heart J 1993; 14: 1531–5.

    Article  PubMed  CAS  Google Scholar 

  154. Saltiel E, Ellrodt AG, Monk JP, et al. Felodipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs 1989; 36: 387–428.

    Article  Google Scholar 

  155. Todd PA, Faulds D. Felodipine: a reappraisal of the pharmacology and therapeutic use of its extended release formulation in cardiovascular disorders. Drugs 1992; 44: 251–76.

    Article  PubMed  CAS  Google Scholar 

  156. Cook E, Clifton GG, Vargas R, et al. Pharmacokinetics, pharmacodynamics and minimum effective clinical dose of intravenous nicardipine. Clin Pharmacol Ther 1990; 47: 766–18.

    Article  Google Scholar 

  157. Urien S, Albengres E, Comte A, et al. Plasma protein binding and erythrocyte partitioning of nicardipine in vitro. J Cardiovasc Pharmacol 1985; 7: 891–8.

    Article  PubMed  CAS  Google Scholar 

  158. Singh BN, Josephson MA. Clinical pharmacology, pharmacokinetics and haemodynamic effects of nicardipine. Am Heart J 1990; 119: 427–34.

    Article  PubMed  CAS  Google Scholar 

  159. Terakawa M, Tokuma Y, Shishido A, et al. Pharmacokinetics of nilvadipine in healthy volunteers. J Clin Pharmacol 1987; 27: 111–7.

    PubMed  CAS  Google Scholar 

  160. Niwa T, Tokuma Y, Noguchi H. Plasma protein binding of nilvadipine, a new dihydropyridine calcium antagonist in man and dog. Res Commun Chem Pathol Pharmacol 1987; 55: 75–8.

    PubMed  CAS  Google Scholar 

  161. Niecicki A, Huber HJ, Stanislaus F. Pharmakokinetik von Nilvadipin. J Cardiovasc Pharmacol 1992; 20 Suppl. 6: S24–S31.

    Google Scholar 

  162. Honerjäger P, Seibel K. Pharmakodynamik von Nilvadipin, einem neuen Calciumantagonisten aus der Reihe der Dihydropyridine. J Cardiovasc Pharmacol 1992; 20 Suppl. 6: S17–23.

    Google Scholar 

  163. Van Harten J, van Brummelen P, Ooms P, et al. Variability in the pharmacokinetics of nisoldipine as caused by differences in liver blood flow response. J Clin Pharmacol 1989; 29: 714–21.

    PubMed  Google Scholar 

  164. Ahr G, Wingender W, Kuhlmann J. Pharmacokinetics of nisoldipine. In: Hugenholtz PG, Meyer, editors. Nisoldipine. Heidelberg: Springer-Verlag, 1987: 59–66.

    Chapter  Google Scholar 

  165. Van Harten J, Burggraaf J, Ligthart GJ, et al. Single- and multiple-dose nisoldipine kinetics and effects in the young, the middle-aged, and the elderly. Clin Pharmacol Ther 1989; 45: 600–7.

    Article  PubMed  Google Scholar 

  166. Baksi AK, Edwards JS, Ahr G. Acomparison of the pharmacokinetics of nisoldipine in elderly and young subjects. Br J Clin Pharmacol 1991; 31: 367–70.

    Article  PubMed  CAS  Google Scholar 

  167. Van Harten J, Burggraaf J, Van Brummelen P, et al. Influence of renal function on the pharmacokinetics and cardiovascular effects of nisoldipine after single and multiple dosing. Clin Pharmacokinet 1989; 16: 55–64.

    Article  PubMed  Google Scholar 

  168. Schran HF, Jaffe JM, Gonasum LM. Clinical pharmacokinetics of isradipine. Am J Med 1988; 84 Suppl. 3B: 80–9.

    Article  Google Scholar 

  169. Fitton A, Benfield P. Isradipine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in cardiovascular disease. Drugs 1990; 40: 31–74.

    Article  PubMed  CAS  Google Scholar 

  170. Leblanc N, Wilde DW, Keef KD, et al. Electrophysiological mechanisms of minoxidil sulfate-induced vasodilation of rabbit portal vein. Circ Res 1989; 65: 1102–11.

    Article  PubMed  CAS  Google Scholar 

  171. Westfall D, Gerthoffer WT. Vasodilators. In: Brody TM, Lamer J, Minneman KP, editors. Human pharmacology. 2nd ed. St Louis: Mosby, 1995: 215–23.

    Google Scholar 

  172. Tarazi RC, Dustan HP, Bravo EL, et al. Vasodilating drugs: contrasting haemodynamic effects. Clin Sci 1976; 51 Suppl.: 573–8.

    Google Scholar 

  173. Campese VM, Stein D, DeQuatro V. Treatment of severe hypertension with minoxidil: advantages and limitations. J Clin Pharmacol 1979; 19: 231–41.

    PubMed  CAS  Google Scholar 

  174. Devine BL, Fife R, Trust PM. Minoxidil, in severe hypertension after failure of other hypotensive drugs. BMJ 1977; II: 667–9.

    Article  Google Scholar 

  175. Pennisis AJ, Takahashi M, Bernstein BH, et al. Minoxidil therapy in children with severe hypertension. Paediatr Pharmacol Ther 1977; 90: 813.

    Google Scholar 

  176. Hull AR, Long DL, Prati RC, et al. The control of hypertension in patients undergoing regular maintenance hemodialysis. Kidney Int 1975; 7 Suppl. 2: 184–7.

    Google Scholar 

  177. Pettinger WA, Mitchell HC. Minoxidil: an alternative to nephrectomy for refractory hypertension. N Engl J Med 1973; 289: 167–73.

    Article  PubMed  CAS  Google Scholar 

  178. Toto RD, Mitchell HC, Pettinger WA. Treatment of hypertension in nondiabetic renal disease. Curr Opin Nephrol Hypertension 1994; 3: 279–85.

    Article  CAS  Google Scholar 

  179. Fagard R, Lijnen P, Staessen J, et al. Mechanical and other factors relating to left ventricular hypertrophy. Blood Press 1994; 1 Suppl.: 5–10.

    Google Scholar 

  180. Lowenthal DT, Affrime MB. Pharmacology and pharmacokinetics of minoxidil. J Cardiovasc Pharmacol 1980; 2 Suppl. 2: 93–106.

    Article  Google Scholar 

  181. Keusch GW, Weidmann P, Campese V, et al. Minoxidil therapy in refractory hypertension: analysis of 155 patients. Nephron 1978; 21: 1–15.

    Article  PubMed  CAS  Google Scholar 

  182. Fleishaker JC, Andreadis NA, Welshman IR, et al. The pharmacokinetics of 2.5- to 10mg oral doses of minoxidil in healthy volunteers. J Clin Pharmacol 1989; 29: 162–7.

    PubMed  CAS  Google Scholar 

  183. Campese VM. Minoxidil: a review of its pharmacological properties and therapeutic use. Drugs 1981; 22: 257–78.

    Article  PubMed  CAS  Google Scholar 

  184. Alleyne GAO, Westerman RL, Nicholson GD, et al. Minoxidil in the treatment of severe and moderate hypertension. Excerpta Med Int Congr Ser 1980; 496: 86–91.

    Google Scholar 

  185. Alpert MA, Bauer JH. Rapid reduction of severe hypertension with minoxidil. Clin Res 1981; 29: 354a.

    Google Scholar 

  186. Alpert MA, Bauer JH, Neviackas JA. Acute reduction of life-threatening blood pressure elevation with minoxidil. Clin Res 1980; 28: 328.

    Google Scholar 

  187. Atkins JM, Mitchell HC, Pettinger WA. Increased pulmonary vascular resistance with systemic hypertension: effect of minoxidil and other antihypertensive agents. Am J Cardiol 1977; 39: 802–7.

    Article  PubMed  CAS  Google Scholar 

  188. Dargie HJ, Dollery CT, Daniel J. Minoxidil in resistant hypertension. Lancet 1977; II: 515–8.

    Article  Google Scholar 

  189. Bennett WM, Golper TA, Muther RS, et al. Efficacy of minoxidil in the treatment of severe hypertension in systemic disorders. J Cardiovasc Pharmacol 1980; Suppl. 2: 142–8.

    Article  Google Scholar 

  190. Rao PS. Long-term oral diazoxide therapy for pulmonary vascular obstructive disease associated with congenital heart defects. Am Heart J 1990; 119: 1317–21.

    Article  PubMed  CAS  Google Scholar 

  191. Chan NS, McLay J, Kenmure AC. Reversibility of primary pulmonary hypertension during six years of treatment with oral diazoxide. Br Heart J 1987; 57: 207–9.

    Article  PubMed  CAS  Google Scholar 

  192. Deal JE, Barratt TM, Dillon MJ. Management of hypertensive emergencies. Arch Dis Child 1992; 67: 1089–92.

    Article  PubMed  CAS  Google Scholar 

  193. Paterson-Brown S, Robson SC, Redfern N, et al. Hydralazine boluses for the treatment of severe hypertension in pre-eclampsia. Br J Obstet Gynaecol 1994; 101: 409–13.

    Article  PubMed  CAS  Google Scholar 

  194. Gogia H, Mehra A, Parikh S, et al. Prevention of tolerance to hemodynamic effects of nitrates with concomitant use of hydralazine in patients with chronic heart failure. J Am Coll Cardiol 1995; 26: 1575–80.

    Article  PubMed  CAS  Google Scholar 

  195. Francis GS, Cohn JN, Johnson G, et al. Plasma norepinephrine, plasma renin activity, and congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II: the V-HeFT VA Cooperative Studies Group. Circulation 1993; 87 Suppl. 6: V140–8.

    Google Scholar 

  196. Verma SP, Silke B, Reynolds GW, et al. Vasodilator therapy for acute heart failure: haemodynamic comparison of hydralazine/isosorbide, alpha-adrenoceptor blockade, and angiotensin-converting enzyme inhibition. J Cardiovasc Pharmacol 1992; 20: 274–81.

    Article  PubMed  CAS  Google Scholar 

  197. Pearson RM. Pharmacokinetics and response to diazoxide in renal failure. Clin Pharmacokinet 1977; 2: 198–204.

    Article  PubMed  CAS  Google Scholar 

  198. Mulrow JP, Crawford MH. Clinical pharmacokinetics and therapeutic use of hydralazine in congestive heart failure. Clin Pharmacokinet 1989; 16: 86–9.

    Article  PubMed  CAS  Google Scholar 

  199. Pruitt AW, Faraj BA, Dayton BG. Metabolism of diazoxide in man and experimental animals. J Pharmacol Exp Ther 1974; 188: 248–56.

    PubMed  CAS  Google Scholar 

  200. Ludden TM, Rotenberg KS, Ludden LK, et al. Relative bioavailability of immediate- and sustained-release hydralazine formulation. J Pharm Sci 1988; 77: 1026–32.

    Article  PubMed  CAS  Google Scholar 

  201. Burch HB, Clement S, Sokol MS, et al. Reactive hypoglycemic coma due to insulin autoimmune syndrome: case report and literature review. Am J Med 1992; 92: 681–5.

    Article  PubMed  CAS  Google Scholar 

  202. Rotenstein D, Serbin S, Welsh T. Palliative treatment of hyperinsulinism with cyproheptadine and diazoxide. Pediatrics 1992; 90: 212–5.

    PubMed  CAS  Google Scholar 

  203. Roschlau G, Baumgarten R, Fengler JD. Dihydralazine hepatitis: morphologic and clinical criteria for diagnosis. Zentralbl Pathol 1990; 136: 127–34.

    CAS  Google Scholar 

  204. Ram CV. Management of hypertensive emergencies: changing therapeutic options. Am Heart J 1991; 122: 356–63.

    Article  PubMed  CAS  Google Scholar 

  205. Hofstra AH, Matassa LC, Uetrecht JP. Metabolism of hydralazine by activated leukocytes: implications for hydralazineinduced lupus. J Rheumatol 1991; 18: 1673–80.

    PubMed  CAS  Google Scholar 

  206. Torffvit O, Thysell H, Nassberger L. Occurrence of autoantibodies directed against myeloperoxydase and elastase in patients treated with hydralazine and presenting with glomerulonephritis. Hum Exp Toxicol 1994; 13: 563–7.

    Article  PubMed  CAS  Google Scholar 

  207. Thomas TJ, Seibold JR, Adams LE, et al. Hydralazine induces Z-DNA conformation in a polynucleotide and elicits anti(ZDNA) antibodies in treated patients. Biochem J 1993; 294: 419–25.

    PubMed  CAS  Google Scholar 

  208. Ganten D, Manwen J, Hellmann T, et al. Das Renin-Angiotensin-System. Neue Aspekte zur Molekularbiologie, Lokalisation und Regulation. Nieren-Hochdruckkr 1989; 18: 48–54.

    CAS  Google Scholar 

  209. Valloton MB. The renin-angiotensin system. Trends Pharmacol Sci 1987; 8: 69–74.

    Article  Google Scholar 

  210. Rang HP, Dale MM, Ritter JM. Bradykinin: pharmacology. Edinburgh: Churchill Livingstone, 1995: 238–40.

    Google Scholar 

  211. Tielemans C, Madhoun P, Lenaers M, et al. Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors. Kidney Int 1990; 38: 982–4.

    Article  PubMed  CAS  Google Scholar 

  212. Vertes V, Haynie R. Comparative pharmacokinetics of captopril, enalapril, and quinapril. Am J Cardiol 1992; 69: 8C–16C.

    Article  PubMed  CAS  Google Scholar 

  213. Belz GG, Kirch W, Kleinbloesem CH. Angiotensin-converting enzyme inhibitors. Relationship between pharmacodynamics and pharmacokinetics. Clin Pharmacokinet 1988; 15: 295–318.

    Article  PubMed  CAS  Google Scholar 

  214. Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329: 1456–62.

    Article  PubMed  CAS  Google Scholar 

  215. Anlauf M. ACE-Hemmer In: Schwabe U, Pfaffrath D, editors. Arzneiverordnungs-Report 95. Stuttgart: Gustav Fischer Verlag, 1995: 18–24.

    Google Scholar 

  216. Linz W, Scholkens BA. A specific β2-bradykinin receptor antagonist HOE140 abolishes the antihypertrophic effect of ramipril. Br J Pharmacol 1992; 105: 771–2.

    Article  PubMed  CAS  Google Scholar 

  217. Regoli D, Rhaleb NE, Dion S, et al. New selective bradykinin receptor antagonists and bradykinin B2 receptor characterisation. Trends Pharmacol Sci 1990; 11: 156–61.

    Article  PubMed  CAS  Google Scholar 

  218. Jalil JE, Janicki JS, Pick R, et al. Coronary vascular remodeling and myocardial fibrosis in the rat with renovascular hypertension. Response to captopril. Am J Hypertens 1991; 4: 51–5.

    PubMed  CAS  Google Scholar 

  219. Brilla CG, Janicki JS, Weber KT. Cardioreparative effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy. Circulation 1991; 83: 1771–9.

    Article  PubMed  CAS  Google Scholar 

  220. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement Trial. N Engl J Med 1992; 327: 669–77.

    Article  PubMed  CAS  Google Scholar 

  221. Ball SG. Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effects of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993; 342: 821–8.

    Google Scholar 

  222. Ray S, Oargie H. Infarct-related heart failure: the choice of ACE-inhibitor does not matter. Cardiovasc Drugs Ther 1994; 8: 433–6.

    Article  PubMed  CAS  Google Scholar 

  223. Hoyer J, Schulte KL, Lenz T. Clinical pharmacokinetics of angiotensin converting enzyme (ACE) inhibitors in renal failure. Clin Pharmacokinet 1993; 24: 230–54.

    Article  PubMed  CAS  Google Scholar 

  224. Blum RA, Olson SC, Kohli RK, et al. Pharmacokinetics of quinapril and its active metabolite, quinaprilat, in patients on chronic hemodialysis. J Clin Pharmacol 1990; 30: 938–42.

    PubMed  CAS  Google Scholar 

  225. Fillastre JP, Moulin B, Godin M, et al. Pharmacokinetics of cilazapril in patients with renal failure. Br J Clin Pharmacol 1989; 27 Suppl. 2: 275S–82S.

    Article  Google Scholar 

  226. Osterziel KJ, Nagel F, Dietz R. Therapie mit ACE-Hemmern bei chronischer Herzinsuffizienz und eingeschränkter Nierenfunktion. Z Kardiol 1994; 83 Suppl. 4: 81–7.

    Google Scholar 

  227. Shionoiri H. Pharmacokinetic drug interactions with ACE inhibitors. Clin Pharmacokinet 1993; 25: 20–58.

    Article  PubMed  CAS  Google Scholar 

  228. Duchin KL, McKinstry DN, Cohen AI, et al. Pharmacokinetics of captopril in healthy subjects and in patients with cardiovascular diseases. Clin Pharmacokinet 1988; 14: 241–59.

    Article  PubMed  CAS  Google Scholar 

  229. Kripalani KJ, McKinstry DN, Singhvi SM, et al. Disposition of captopril in normal subjects. Clin Pharmacol Ther 1980; 27: 636–41.

    Article  PubMed  CAS  Google Scholar 

  230. Brogden RN, Todd PA, Sorkin EM. Captopril: an update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs 1988; 36: 540–600.

    Article  PubMed  CAS  Google Scholar 

  231. Williams GM, Sugerman AA. The effect of a meal, at various times relative to drug administration, on the bioavailability of captopril [abstract]. J Clin Pharmacol 1982; 22: 18.

    Google Scholar 

  232. Creasey WA, Funke PT, McKinstry DN, et al. Pharmacokinetics of captopril in elderly healthy male volunteers. J Clin Pharmacol 1986; 26: 264–8.

    PubMed  CAS  Google Scholar 

  233. Cody RJ, Covit A, Schaer G, et al. Captopril pharmacokinetics in chronic heart failure: correlation with acute hemodynamic and hormonal response. Clin Pharmacol Ther 1982; 31: 211.

    Google Scholar 

  234. Drummer OH, Workman BS, Miach PJ, et al. The pharmacokinetics of captopril and captopril disulfide conjugates in uraemic patients on maintenance dialysis: comparison with patients with normal renal function. Eur J Clin Pharmacol 1987; 32: 267–71.

    Article  PubMed  CAS  Google Scholar 

  235. Hirakata H, Onoyama K, Iseki K, et al. Worsening of anaemia induced by long-term use of captopril in hemodialysis patients. Am J Nephrol 1984; 4: 355–60.

    Article  PubMed  CAS  Google Scholar 

  236. Pierides AM, Rommel AJ, Heald A, et al. Captopril elimination during hemodialysis and in chronic renal failure. Trans Am Soc Artific Org 1980; 9: 59.

    Google Scholar 

  237. Shotan A, Widexhorn I, Hurst A, et al. Risks of angiotensin converting enzyme inhibition during pregnancy, experimental and clinical evidence, potential mechanisms, and recommendations for use. Am J Med 1994; 96: 451–6.

    Article  PubMed  CAS  Google Scholar 

  238. Devlin RG, Fleiss PM. Captopril in human blood and breast milk. J Clin Pharmacol 1981; 21: 110–3.

    PubMed  CAS  Google Scholar 

  239. Pereira CM, Tam YK, Collins-Nakai RL. The pharmacokinetics of captopril in infants with congestive heart failure. Ther Drug Monit 1991; 13: 209–14.

    Article  PubMed  CAS  Google Scholar 

  240. De Bock V, Mets T, Romagnoli M, et al. Captopril treatment of chronic heart failure in the very old. J Gerontol 1994; 49: M148–52.

    PubMed  Google Scholar 

  241. Mäntylä R, Männistö PT, Vuorela A, et al. Impairment of captopril bioavailability by concomitant food and antacid intake. Int J Clin Pharmacol Ther Toxicol 1984; 22: 626–9.

    PubMed  Google Scholar 

  242. Tocco DJ, de Luna FA, Duncan AEW, et al. The physiological disposition and metabolism of enalapril maleate in laboratory animals. Drug Metab Dispos 1982; 10: 15–9.

    PubMed  CAS  Google Scholar 

  243. Todd PA, Goa KL. Enalapril: a reappraisal of its pharmacology and therapeutic use in hypertension. Drugs 1992; 43: 346–81.

    Article  PubMed  CAS  Google Scholar 

  244. Swanson BN, Vlasses PH, Ferguson RK, et al. Influence of food on the bioavailability of enalapril. J Pharm Sci 1984; 73: 1655–7.

    Article  PubMed  CAS  Google Scholar 

  245. MacFadyen RJ, Meredith PA, Elliott HL. Enalapril clinical pharmacokinetics and pharmacokinetic-pharmacodynamic relationships. Clin Pharmacokinet 1993; 25: 274–82.

    Article  PubMed  CAS  Google Scholar 

  246. Mujais SK, Quintanilla A, Zahid M, et al. Renal handling of enalaprilat. Am J Kidney Dis 1992; 19: 121–5.

    PubMed  CAS  Google Scholar 

  247. Ulm EH, Hichens M, Gomez HJ, et al. Enalapril maleate and a lysine analogue (MK-521): disposition in man. Br J Clin Pharmacol 1982; 14: 357–62.

    Article  PubMed  CAS  Google Scholar 

  248. Lowenthal DT, Irvin JD, Merrill BA, et al. The effect of renal function on enalapril kinetics. Clin Pharmacol Ther 1985; 38: 661–6.

    Article  PubMed  CAS  Google Scholar 

  249. Hersh AD, Kelly JG, Laher MS, et al. Effect of hydrochlorothiazide on the pharmacokinetics of enalapril in hypertensive patients with varying renal function. J Cardiovasc Pharmacol 1996; 27: 7–11.

    Article  PubMed  CAS  Google Scholar 

  250. Kelly JG, Doyle GD, Carmody M, et al. Pharmacokinetics of lisinopril, enalapril and enalaprilat in renal failure: effects of haemodialysis. Br J Clin Pharmacol 1988; 26: 781–6.

    Article  PubMed  CAS  Google Scholar 

  251. Baba T, Murabayashi S, Tomiyama T, et al. The pharmacokinetics of enalapril in patients with compensated liver cirrhosis. Br J Clin Pharmacol 1990; 29: 766–9.

    Article  PubMed  CAS  Google Scholar 

  252. Miller K, Atkin B, Rodel Jr PV, et al. Enalapril: a well tolerated and efficacious agent for the pediatric hypertensive patient. J Cardiovasc Pharmacol 1987; 10 Suppl. 7: S154–6.

    Article  Google Scholar 

  253. Macdonald NJ, Sioufi A, Howie CA, et al. The effects of age on the pharmacokinetics and pharmacodynamics of single oral doses of benazepril and enalapril. Br J Clin Pharmacol 1993; 36: 205–9.

    Article  PubMed  CAS  Google Scholar 

  254. Hockings N, Ajayi AA, Reid JL. Age and the pharmacokinetics of angiotensin converting enzyme inhibitors enalapril and enalaprilat. Br J Clin Pharmacol 1986; 21: 341–8.

    Article  PubMed  CAS  Google Scholar 

  255. Verho M, Luck C, Stelter WJ, et al. Pharmacokinetics, metabolism and biliary and urinary excretion of oral ramipril in man. Curr Med Res Opin 1995; 13: 264–73.

    Article  PubMed  CAS  Google Scholar 

  256. Mannhold R. Ramipril. Drugs Future 1985; 10: 400–4.

    Google Scholar 

  257. Todd PA, Benfield P. Ramipril: a review of its pharmacological properties and therapeutic efficacy in cardiovascular disorders. Drugs 1990; 39: 110–35.

    Article  PubMed  CAS  Google Scholar 

  258. Meisel S, Shamiss A, Rosenthal T. Clinical pharmacokinetics of ramipril. Clin Pharmacokinet 1994; 26: 7–15.

    Article  PubMed  CAS  Google Scholar 

  259. Ball SG, Robertson JIS. Clinical pharmacology of ramipril. Am J Cardiol 1987; 59: 23D–7D.

    Article  PubMed  CAS  Google Scholar 

  260. Shionori H, Ikeda Y, Kimura K, et al. Pharmacodynamics and pharmacokinetics of single-dose ramipril in hypertensive patients with various degrees of renal function. Curr Ther Res 1986; 40: 74–85.

    Google Scholar 

  261. Schunkert H, Kindler J, Gassmann MN, et al. Steady-state kinetics of ramipril in renal failure. J Cardiovasc Pharmacol 1989; 13 Suppl. 3: S52–4.

    Article  Google Scholar 

  262. Meyer BH, Müller FO, Badian M, et al. Pharmacokinetics of ramipril in the elderly. Am J Cardiol 1987; 59: 33D–3D.

    Article  PubMed  CAS  Google Scholar 

  263. Gilchrist WJ, Beard K, Manhem P, et al. Pharmacokinetics and effects on the renin-angiotensin system of ramipril in elderly patients. Am J Cardiol 1987; 59: 28D–32D.

    Article  PubMed  CAS  Google Scholar 

  264. Boeijinga JK, Matroos AW, Van Maarschalkerweerd MW, et al. No interactions shown between ramipril and coumarine derivatives. Curr Ther Res 1988; 44: 902–8.

    Google Scholar 

  265. Verho M, Malerczyk V, Grötsch H, et al. Absence of interaction between ramipril, a new ACE-inhibitor, and phenprocoumon, an anticoagulant agent. Pharmatherapeutica 1989; 5: 392–9.

    PubMed  CAS  Google Scholar 

  266. Garavaglia GE, Messerli FH, Nunez BD, et al. Immediate and short-term cardiovascular effects of a new converting enzyme inhibitor (lisinopril) in essential hypertension. Am J Cardiol 1988; 62: 912–6.

    Article  PubMed  CAS  Google Scholar 

  267. Giles TD, Katz R, Sullivan JM, et al. Short- and long-acting angiotensin-converting enzyme inhibitors: a randomized trial of lisinopril versus captopril in the treatment of congestive heart failure. J Am Coll Cardiol 1989; 13: 1240–7.

    Article  PubMed  CAS  Google Scholar 

  268. Beermann B. Pharmacokinetics of lisinopril. Am J Med 1988; 85: 25–30.

    Article  PubMed  CAS  Google Scholar 

  269. Thomson AH, Kelly JG, Whiting B. Lisinopril population pharmacokinetics in elderly and renal disease patients with hypertension. Br J Clin Pharmacol 1989; 27: 57–65.

    Article  PubMed  CAS  Google Scholar 

  270. Lancaster SG, Todd PA. Lisinopril: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs 1988; 35: 646–69.

    Article  PubMed  CAS  Google Scholar 

  271. Till AE, Dickstein K, Aarsland T, et al. The pharmacokinetics of lisinopril in hospitalized patients with congestive heart failure. Br J Clin Pharmacol 1989; 27: 199–204.

    Article  PubMed  CAS  Google Scholar 

  272. Gibson TP, Shaw WC, Koch KM, et al. Pharmacokinetics of lisinopril in renal insufficiency. J Clin Pharmacol 1986; 26: 544.

    Google Scholar 

  273. Van Schaik BA, Geyskes GG, Van der Wouw PA, et al. Pharmacokinetics of lisinopril in hypertensive patients with normal and impaired renal function. Eur J Clin Pharmacol 1988; 34: 61–5.

    Article  PubMed  Google Scholar 

  274. Droste HT, deVries RA. Chronic hepatitis caused by lisinopril. Neth J Med 1995; 46: 95–8.

    Article  PubMed  CAS  Google Scholar 

  275. Hagley MT, Hulisz DT, Burns CM. Hepatotoxicity associated with angiotensin-converting enzyme inhibitors. Ann Pharmacotherapy 1993; 27: 228–31.

    CAS  Google Scholar 

  276. Gautam PC, Vargas E, Lye M. Pharmacokinetics of lisinopril (MK521) in healthy young and elderly subjects and in elderly patients with cardiac failure. J Pharm Pharmacol 1987; 39: 929–31.

    Article  PubMed  CAS  Google Scholar 

  277. Gomez HJ, Cirillo VJ, Moncloa F. The clinical pharmacology of lisinopril. J Cardiovasc Pharmacol 1987; 9 Suppl 3.: 527–34.

    Google Scholar 

  278. Fabris B, Chen B, Pupic V, et al. Inhibition of angiotensinconverting enzyme (ACE) in plasma and tissue. J Cardiovasc Pharmacol 1990; 15 Suppl. 2: S6–13.

    Article  Google Scholar 

  279. Os I, Bratland B, Dahlof B, et al. Effect and tolerability of combining lovastatin with nifedipine or lisinopril. Am J Hypertens 1993; 6: 688–92.

    PubMed  CAS  Google Scholar 

  280. Laher MS, Mulkerrins E, Hosie J, et al. The effects of age and renal impairment on the pharmacokinetics of co-administered lisinopril and hydrochlorothiazide. J Hum Hypertens 1991; 5 Suppl. 22: 77–84.

    Google Scholar 

  281. Wadworth AN, Brogden RN. Quinapril: a review of its pharmacological properties and therapeutic efficacy in cardiovascular disorders. Drugs 1991; 41: 378–99.

    Article  PubMed  CAS  Google Scholar 

  282. Sedman AG, Posvar E. Clinical pharmacology of quinapril in healthy volunteers and in patients with hypertension and congestive heart failure. Angiology 1989; 40: 360–9.

    PubMed  CAS  Google Scholar 

  283. Vertes V, Haynie R. Comparative pharmacokinetics of captopril, enalapril, and quinapril. Am J Cardiol 1992; 69: 8C–16C.

    Article  PubMed  CAS  Google Scholar 

  284. Begg EJ, Robson RA, Bailey RR, et al. The pharmacokinetics and pharmacodynamics of quinapril and quinaprilat in renal impairment. Br J Clin Pharmacol 1990; 30: 213–20.

    Article  PubMed  CAS  Google Scholar 

  285. Swartz RD, Starmann B, Horvath AM, et al. Pharmacokinetics of quinapril and its active metabolite quinaprilat during continuous ambulatory peritoneal dialysis. J Clin Pharmacol 1990; 30: 1136–41.

    PubMed  CAS  Google Scholar 

  286. Wolter K, Fritschka E. Pharmacokinetics and pharmacodynamics of quinaprilat after low dose quinapril in patients with terminal renal failure. Eur J Clin Pharmacol 1993; 44 Suppl. 1: S53–6.

    Article  Google Scholar 

  287. Neub M, Vollmer KO, Anderton J, et al. Pharmacokinetics of the ACE inhibitor quinapril in young and elderly volunteers. Eur J Clin Pharmacol 1989; 36 Suppl.: A222.

    Google Scholar 

  288. Begg EJ, Robson RA, Ikram H, et al. The pharmacokinetics of quinapril and quinaprilat in patients with congestive heart failure. Br J Clin Pharmacol 1994; 37: 302–4.

    Article  PubMed  CAS  Google Scholar 

  289. Frank GJ, Knapp LE, McLain RW. Overall tolerance and safety of quinapril in clinical trials. Angiology 1989; 40: 405–15.

    PubMed  CAS  Google Scholar 

  290. Todd PA, Heel RC. Enalapril: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs 1986; 31: 198–248.

    Article  PubMed  CAS  Google Scholar 

  291. Opie LH. Individualised selection of antihypertensive therapy. Drugs 1993; 46 Suppl. 2: 142–8.

    Article  Google Scholar 

  292. Lee RJ, Wexler RR, Saye JAM, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 1993; 45: 205–51.

    PubMed  Google Scholar 

  293. Morgan HE, Baker KM. Cardiac hypertrophy: mechanical, neural and endocrine dependance. Circulation 1991; 83: 13–25.

    Article  PubMed  CAS  Google Scholar 

  294. Baker KM, Dostal DE, Chemin MI, et al. Angiotensin II-mediated cardiac hypertrophy in adult rats. J Cell Biochem 1991; 15C: 167.

    Google Scholar 

  295. Murphy DD, Shepard J, Smith SG, et al. Effects of the AT1 receptor antagonist losartan on angiotensin II induced hypertrophy of rat cardiomyocytes. FASEB J 1992; 6: A1261.

    Google Scholar 

  296. Dahlof B. Effect of angiotensin II blockade on cardiac hypertrophy and remodelling: a review. J Hum Hypertens 1995; 9 Suppl. 5: S37–44.

    Google Scholar 

  297. Goldberg AI, Dunlay MC, Sweet CS. Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. J Cardiol 1995; 75: 793–5.

    Article  CAS  Google Scholar 

  298. Crozier I, Ikram H, Awan N, et al. Losartan in heart failure: hemodynamic effects and tolerability. Circulation 1995; 91: 691–7.

    Article  PubMed  CAS  Google Scholar 

  299. Wong PC, Quanml, Saye JM, et al. Pharmacology of XR510, a potent orally active nonpeptide angiotensin II AT1 receptor antagonist with high affinity for the ATS receptor subtype. J Cardiovasc Pharmacol 1995; 26: 354–62.

    Article  PubMed  CAS  Google Scholar 

  300. Chang LL, Ashton WT, Flanagan KL, et al. Potent and orally active angiotensin II receptor antagonists with equal affinity for human AT1 and AT2 subtypes. J Med Chem 1995; 38: 3741–58.

    Article  PubMed  CAS  Google Scholar 

  301. Wong PC, Price WA, Chiu AT, et al. Non-peptide angiotensin II receptor antagonists: XI: pharmacology of EXP3174, an active metabolite of DuP753, an orally active hypertensive agent. J Pharmacol Exp Ther 1990; 255: 211–7.

    PubMed  CAS  Google Scholar 

  302. Lo MW, Goldberg MR, McCrea JB, et al. Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans. Clin Pharmacol Ther 1995; 58: 641–9.

    Article  PubMed  CAS  Google Scholar 

  303. Christ DD. Human plasma protein binding of the angiotensin II receptor antagonist losartan potassium and its pharmacological active metabolite EXP3174. J Clin Pharmacol 1995; 35: 515–20.

    PubMed  CAS  Google Scholar 

  304. Munafo A, Christen Y, Nussberger J, et al. Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist. Clin Pharmacol Ther 1992; 51: 513–21.

    Article  PubMed  CAS  Google Scholar 

  305. Gradman AH, Arcuri KE, Goldberg AI, et al. A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension. Hypertension 1995; 25: 1345–50.

    Article  PubMed  CAS  Google Scholar 

  306. Weber MA, Byyny RL, Pratt JH, et al. Blood pressure effects of the angiotensin II receptor blocker, losartan. Arch Intern Med 1995; 155: 405–11.

    Article  PubMed  CAS  Google Scholar 

  307. Ohtawa M, Takayama F, Saitoh K, et al. Pharmacokinetics and biochemical efficacy after single and multiple oral administration of losartan, an orally active nonpeptide angiotensin II receptor antagonist, in humans. Br J Clin Pharmacol 1993; 35: 290–7.

    Article  PubMed  CAS  Google Scholar 

  308. Sica DA, Lo MW, Shaw WC, et al. The pharmacokinetics of losartan in renal insufficiency. J Hypertens 1995; 13 Suppl. 1: S49–52.

    Google Scholar 

  309. Chan JCN, Critchley JA, Lappe JT, et al. Randomised, doubleblind, parallel study of the anti-hypertensive efficacy and safety of losartan potassium compared with felodipine ER in elderly patients with mild to moderate hypertension. J Hum Hypertens 1995; 9: 765–71.

    PubMed  CAS  Google Scholar 

  310. Nakashima M, Uematsu T, Kosuge K, et al. Pilot study of the uricosuric effect of DuP-753, a new angiotensin II receptor antagonist, in healthy subjects. Eur J Clin Pharmacol 1992; 42: 333–5.

    Article  PubMed  CAS  Google Scholar 

  311. Lacourciere Y, Lefebvre J. Modulation of the renin-angiotensinaldosterone system and cough. Can J Cardiol 1995; 11 Suppl. F: 33F–9F.

    Google Scholar 

  312. Goldberg MR, Lo MW, Bradstreet TE, et al. Effects of cimetidine on pharmacokinetics and pharmacodynamics of losartan, an AT1-selective non-peptide angiotensin II receptor antagonist. Eur J Clin Pharmacol 1995; 49: 115–9.

    Article  PubMed  CAS  Google Scholar 

  313. Kong AT, Tomasko L, Waldman SA, et al. Losartan does not affect the pharmacokinetics and pharmacodynamics of warfarin. J Clin Pharmacol 1995; 35: 1008–15.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology, University of Frankfurt, 60590, Frankfurt, Germany

    Roland Kirsten & Karen Nelson

  2. Department of Internal Medicine, University of Jena, Jena, Germany

    Daniel Kirsten

  3. Department of Internal Medicine II, Technical University of Aachen, Aachen, Germany

    Bernhard Heintz

Authors
  1. Roland Kirsten
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel Kirsten
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernhard Heintz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kirsten, R., Nelson, K., Kirsten, D. et al. Clinical Pharmacokinetics of Vasodilators. Clin Pharmacokinet 34, 457–482 (1998). https://doi.org/10.2165/00003088-199834060-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199834060-00003

Keywords

Search

Navigation