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Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects

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Summary

The pharmacokinetics of bupropion hydrochloride, a structurally novel antidepressant agent, have been studied in healthy male and female subjects following administration of single oral doses of 50, 100 and 200 mg. Plasma drug concentrations were determined directly by a specific radioimmunoassay (r. i. a.), while urinary measurements required a prior solvent extraction to remove substances interfering in the assay. Bupropion appeared rapidly in the plasma, suggesting good absorption. Drug plasma concentration-time data were fitted well to a two-compartment open model of drug disposition by use of the computer program NONLIN. By comparison of AUC, Cmax and tmax values, the pharmacokinetics of bupropion were found to be linear across the 50–200 mg dose range in both sexes. When the data were normalized for subjects' body weights, no differences between pharmacokinetic parameters for male and female subjects were found. Mean disposition half-lives across treatments were 1.2–1.4 h for t1 2α and 10.7–13.8 h for the t1 2β. Bupropion was extensively bound (85%) to human plasma proteins over a wide drug concentration range. Less than 1% of a 200 mg oral dose of bupropion hydrochloride appeared in the urine of 16 subjects as unchanged drug, indicating extensive metabolism of the parent compound.

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References

  1. Mehta NB US Patent 3,819,706 (1974); US Patent 3,885,046 (1975)

  2. Soroko F, Mehta NB, Garvey M, Ravo J (1970) Pharmacology of d,1-α-t-butylamino-3-chloropropiophenone HCl. Fed Proc 29: 650

    Google Scholar 

  3. Soroko FE, Mehta NB, Maxwell RA, Ferris RM, Schroeder DH (1977) Bupropion hydrochloride (± α-τ-butylamino-3-chloropropiophenone): a novel antidepressant agent. J Pharm Pharmacol 29: 767–770

    Google Scholar 

  4. Soroko FE, Maxwell RA (1978) The CNS pharmacology of bupropion HCl (Wellbatrin®), a novel antidepressant agent. Fed Proc 37: 481

    Google Scholar 

  5. Ferris RM, White H, Russell A, Beaman OJ, Maxwell RA (1978) The effects of bupropion HCl on uptake of biogenic amines and an inhibition of MAO. Fed Proc 37: 481

    Google Scholar 

  6. Leighton HJ, Maxwell RA (1978) The autonomic and cardiovascular pharmacology of bupropion HCl. Fed Proc 37: 481

    Google Scholar 

  7. Kuhn R (1958) The treatment of depressive states with G22355 (imipramine hydrochloride). Am J Psychiatry 115: 459–464

    Google Scholar 

  8. Hollister LE (1972) Clinical use of psychotherapeutic drugs II: antidepressant and antianxiety drugs and special problems in the use of psychotherapeutic drugs. Drugs 4: 363–410

    Google Scholar 

  9. Jefferson JW (1975) A review of the cardiovascular effects and toxicity of tricyclic antidepressants. Psychosom Med 37: 160–179

    Google Scholar 

  10. Fann WE, Schroeder DH, Mehta NB, Maxwell RA (1974) Wellbatrin in the treatment of depression. Pharmacologist 16: 264

    Google Scholar 

  11. Fann WE, Schroeder DH, Mehta NB, Soroko FE, Maxwell RA (1978) Clinical trial of bupropion HCl in treatment of depression. Curr Ther Res 23: 222–229

    Google Scholar 

  12. Fabre LF, (Jr), McLendon D, Mallette A (1977) A double-blind clinical trial of bupropion HCl — a novel antidepressant. Clin Pharmacol Ther 21: 102

    Google Scholar 

  13. Butz RF, Schroeder DH, Welch RM, Mehta NB, Phillips AP, Findlay JWA (1981) Radioimmunoassay and pharmacokinetic profile of bupropion in the dog. J Pharmacol Exp Ther 217: 602–610

    Google Scholar 

  14. Metzler CM, Elfring GL, McEwen AJ (1974) A package of computer programs for pharmacokinetic modeling. Biometries30: 562–563

    Google Scholar 

  15. Gibaldi M. Perrier D (1975) Pharmacokineties. Marcel Dekker, New York

    Google Scholar 

  16. Schroeder DH, Eiseman JL, Mehta NB, Brent DA, Soroko FE, Weleh RM (1979) The isolation and identification of some basie urinary metabolities of bupropion HCl in man. Pharmacologist 21: 191

    Google Scholar 

  17. Schroeder DH, Hinton ML, Smith PG, Nichol CA, Welch RM (1978) A method of analysis for bupropion and its disposition in animals and man. Fed Proc 37: 691

    Google Scholar 

  18. Hinton ML, Schroeder DH, Smith PG, Kersh RD, Pillow EM, Brent DA, Welch RM (1980) Metabolism and disposition of11C-bupropion in rats. Pharmacologist 22: 188

    Google Scholar 

  19. Judd CI, Ursella RC (1975) Absorption, distribution, excretion, and metabolism of antidepressants. In: Fielding S, Lal H (eds) Antidepressants. Futura Publishing, New York, pp 231–265

    Google Scholar 

  20. Charalampous KD, Johnson PC (1967) Studies of C14-protriptyline in man: plasma levels and excretion. J Clin Pharmacol 7: 93–96

    Google Scholar 

  21. Garland WA, Min BH (1978) The kinetics of amitriptyline following single oral dose administration to man. Res Commun Chem Pathol Pharmacol 22: 475–484

    Google Scholar 

  22. Eschenhof E, Rieder J (1969) Untersuchungen über das Schicksal des Antidepressivums Amitriptylin im Organismus der Ratte und des Menschen. Arzneim Forsch 19: 957–966

    Google Scholar 

  23. Haydu GG, Dhrymiotis A, Quinn GP (1967) Two varieties of plasma imipramine curves in psychotic depressions and normal controls. Am J Psychiatry 124: 257–260

    Google Scholar 

  24. Alexanderson B (1972) Pharmacokinetics of nortriptyline in man after single and multiple oral doses: the predictability of steady-state plasma concentrations from single-dose plasma level data. Eur J Clin Pharmacol 4: 82–91

    Google Scholar 

  25. Alexanderson B (1972) Pharmacokinetics of desmethylimi-pramine and nortriptyline in man after single and multiple oral doses — a crossover study. Eur J Clin Pharmacol 5: 1–10

    Google Scholar 

  26. Alexanderson B, Borga O, Alván G (1971) The availability of orally administered nortriptyline. Eur J Clin Pharmacol 5: 181–185

    Google Scholar 

  27. Alexanderson B, Evans DAP, Sjöqvist F (1969) Steady-state plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy. Br Med J 4: 764–768

    Google Scholar 

  28. Hammer W, Sjöqvist F (1967) Plasma levels of monomethylated tricyclic antidepressants during treatment with imipramine-like compounds. Life Sci 6: 1895–1903

    Google Scholar 

  29. Riegelman S, Loo JCK, Rowland M (1968) Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J Pharm Sci 57: 117–123

    Google Scholar 

  30. Borga O, Azarnoff DL, Sjöqvist F (1968) Species differences in the plasma protein binding of desipramine. J Pharm Pharmacol 20: 571–573

    Google Scholar 

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Findlay, J.W.A., Van Wyck Fleet, J., Smith, P.G. et al. Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects. Eur J Clin Pharmacol 21, 127–135 (1981). https://doi.org/10.1007/BF00637513

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