Summary
Acutely administered ethanol has been shown to inhibit the hepatic metabolism of a number of drugs. Ethanol might be expected to decrease the first-pass extraction of chlormethiazole leading to higher blood levels of this high clearance sedative frequently used in the management of alcoholic patients. Chlormethiazole has a narrow therapeutic index and the unexpected deaths reported in alcoholics taking this drug may have been due to an effect of ethanol on the metabolism of chlormethiazole. However in this study, acutely administered ethanol maintained at levels around 22 mmol/l had no significant effect on the disposition or elimination of either orally or intravenously administered chlormethiazole.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Sellers EM, Holloway MR (1978) Drug kinetics and alcohol ingestion. Clin Pharmacokinet 3: 440–452
Sellers EM, Naranjo CA, Giles HG, Frecker RC, Khouie V, Beeching M, Fan T (1980) Mechanism of ethanol-diazepam pharmacokinetic interaction. Clin Pharmacol Ther 27: 286
Desmond PV, Patwardham RV, Schenker S, Hoyumpa AM (1980) Short-term ethanol administration impairs the elimination of chlordiazepoxide (Librium) in man. Eur J Clin Pharmacol 18: 275–278
Rubin E, Gang H, Misra P, Lieber CS (1970) Inhibition of drug metabolism by acute ethanol intoxication. Am J Med 49: 801–806
Wilkinson GR, Shand DG (1975) A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 18: 377–389
Horder JM (1977) Fatal chlormethiazole poisoning in chronic alcoholics. Br Med J 2: 614
Shaw G, Bury RW, Mashford ML, Breen KJ, Desmond PV (1981) Cimetidine impairs the elimination of chlormethiazole. Eur J Clin Pharmacol 21: 83–85
Benet LZ, Galeazzi RL (1979) Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci 68: 1071–1073
Runciman WB, Ilsley AH, Mather LE, Upton RN, Carapetis R (1982) A comparison of the effects of general and spinal anaesthesia on chlormethiazole kinetics in the chronically catheterized sheep. Clin Exp Pharmacol Physiol 9: 399
Smythe CM, Heinemann HO, Bradley SE (1953) Estimated hepatic blood flow in the dog: Effect of ethyl alcohol on it, renal blood flow, cardiac output and arterial pressure. Am J Physiol 172: 737–742
Neuvonen PJ, Pentikainen PJ, Jostell KG, Syvalahti E (1981) Effect of ethanol on the pharmacokinetics of chlormethiazole in humans. Int J Clin Pharmacol Ther Toxicol 19: 552–560
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bury, R.W., Desmond, P.V., Mashford, M.L. et al. The effect of ethanol administration on the disposition and elimination of chlormethiazole. Eur J Clin Pharmacol 24, 383–385 (1983). https://doi.org/10.1007/BF00610059
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00610059