Summary
N-Acetylcysteine was given intravenously and as three fast dissolving and one slow-release formulation, on separate occasions, as a single dose of 600 mg to 10 fasting (5 men and 5 women) healthy volunteers. Blood and urine were sampled for the following 12 h.
Renal clearance constituted around 30% of total body clearance, which was 0.21 l/h/kg. Volume of distribution was 0.33 l/kg, consistent with distribution mainly to extracellular water. The late elimination half-life was 2.27 h and the mean residence time 1.62 h.
The slow-release tablet resulted in a flattened plasma concentration-time curve typical of slow release formulations, while the other three oral formulations were rapidly absorbed.
The oral availability of N-acetylcysteine varied between 6 and 10%, with the slow-release tablet having the lowest and the fast dissolving tablet the highest availability.
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References
Sheffner AL (1983) The reduction in vitro in viscosity of mucoprotein solutions by a new mucolytic agent N-acetyl-L-cysteine. Ann NY Acad Sci 106: 298–310
Prescott LF, Illingworth RN, Critchley JAJH, Stewart MJ, Adam RD, Proudfoot AT (1979) Intravenous N-acetylcysteine: The treatment of choice for paracetamol poisoning. Br Med J 2: 1097–1100
Myers C, Bonow R, Palmeri S, Jenkins J, Corden B, Locker G, Doroshow J, Epstein S (1983) A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-Acetylcysteine. Semin Oncol 10 [Suppl 1]: 53–55
Holoye PY, Duelge J, Hansen RM, Anderson T (1983) Prophylaxis, of ifosfamide toxicity with oral acetylcysteine. Semin Oncol 10 [Suppl 1]: 66–71
Botta JA, Nelson LW, Wieker JH Jr (1973) Acetylcysteine in the prevention of cyclophosphamide-induced cystitis in rats. J Natl Cancer Inst 51: 1051–1058
Grassi C, Morandi GC (1976) A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis. Eur J Clin Pharmacol 9: 393–396
Lemy-Debois N, Frigerio G, Lualdi P (1978) Oral acetylcysteine in bronchopulmonary disease. Comparative clinical trial with bromhexine. Acta Therapeut 4: 125–132
Multicenter Study Group (1980) Long-term oral acetylcysteine in chronic bronchitis. A double-blind controlled study. Eur J Respir Dis 61 [Suppl 111]: 93–108
Boman G, Bäcker U, Larsson S, Melander B, Wåhlinder L (1983) Oral acetylcysteine reduces exacerbation rates in chronic bronchitis: Report of a trial organized by the Swedish Society for Pulmonary Diseases. Eur J Respir Dis 64: 405–415
Rodenstein D, De Coster A, Gazzaniga A (1978) Pharmacokinetics of oral acetylcysteine: Absorption, binding and metabolism in patients with respiratory disorders. Clin Pharmacokinet 3: 247–254
Maddock J (1980) Biological properties of acetylcysteine: Assay development and pharmacokinetic studies. Eur J Respir Dis 61 [Suppl 111]: 52–58
Morgan LR, Holdiness MR, Gillen LE (1983) N-Acetylcysteine: Its bioavailability and interaction with ifosfamide metabolites. Semin Oncol 10 [Suppl 1]: 56–61
Frank H, Thiel D, Langer K (1984) Determination of N-acetyl-L-cysteine in biological fluids. J Chromatogr 309: 261–267
Kågedal B, Källberg M, Mårtensson J (1984) Determination of non-protein-bound N-acetylcysteine in plasma by high-performance liquid chromatography. J Chromatogr 311: 170–175
Lewis PA, Woodward AJ, Maddock J (1984) High-performance liquid chromatographic assay for N-acetylcysteine in plasma and urine. J Pharm Sci 73 [7]: 996–998
Borgström L, Johansson C-G, Larsson H, Lenander R (1981) Pharmacokinetics of bendroflumethiazide after low oral doses. J Pharmacokinet Biopharmaceut 9 [4]: 431–441
Kågedal B, Källberg M (1982) Reversed-phase ion-pair high-performance liquid chromatography of mercaptoacetate and N-acetylcysteine after derivatization with N-(1-pyrene)maleimide and N-(7-methylamino-4-methyl-3-coumarinyl)-maleimide. J Chromatogr 229: 409–415
Krenzelok EP, North DS, Peterson RG (1980) The effect of activated charcoal administration on N-acetylcysteine serum levels in human subjects. Vet Hum Toxicol 22 [Suppl 2]: 56–58
Rowland M, Tozer TN (1980) Clinical pharmacokinetics concepts and applications. Lea & Febiger, Philadelphia, p 50
Rowland M, Tozer TN (1980) Clinical pharmacokinetics concepts and applications. Lea & Febiger, Philadelphia, p 149
Bonanomi L, Gazzaniga A (1980) Toxicological, pharmacokinetic and metabolic studies on acetylcysteine. Eur J Respir Dis 61 [Suppl 111]: 45–51
Sheffner AL, Medler EM, Baily KR, Gallo DG, Mueller AJ, Sarett HP (1966) Metabolic studies with acetylcysteine. Biochem Pharmacol 15: 1523–1535
Lauterburg BH, Corcoran GB, Mitchell JR (1983) Mechanism of action of N-acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. J Clin Invest 71: 980–991
Grassi C, Morandini GC, Frigerio G (1973) Clinical evaluation of systemic acetylcysteine by different routes of administration. Curr Ther Res 15: 165–179
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Borgström, L., Kågedal, B. & Paulsen, O. Pharmacokinetics of N-acetylcysteine in man. Eur J Clin Pharmacol 31, 217–222 (1986). https://doi.org/10.1007/BF00606662
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DOI: https://doi.org/10.1007/BF00606662