Home LiteratureArticle Details
PMID: 2861929 Published · ppublish English Journal Article Review

Effects of ethanol on drug and metabolite pharmacokinetics.

Clinical pharmacokinetics ·Vol. 10 ·No. 3 ·1985-00-00 ·Pages 228-47

Lane EA, Guthrie S, Linnoila M

Abstract

Pharmacokinetic interactions of ethanol with other drugs, including its effects upon drug metabolite disposition, are reviewed in terms of clearance concepts. This approach is particularly useful in understanding the mechanisms of ethanol-drug interactions, i.e. in separating the effects of ethanol upon drug clearance, volume of distribution and plasma protein binding. The application of clearance concepts provides the basis for understanding the qualitative differences in ethanol interactions with low and high hepatic extraction ratio drugs. The effects of short and long term ethanol consumption upon different types of drug metabolism (oxidative, acetylation and glucuronidation) have been considered. Long term ethanol consumption may increase the clearance of a drug by induction of oxidative metabolism whereas short term consumption may decrease the clearance of such a drug. Clearance by N-acetylation appears to be increased in the presence of ethanol, and clearance by conjugation to glucuronic acid is decreased for some drugs by single-dose consumption of ethanol.

MeSH Terms
Analgesics/metabolism Anti-Anxiety Agents/metabolism Anti-Arrhythmia Agents/metabolism Anti-Infective Agents/metabolism Biotransformation Drug Interactions Ethanol/pharmacology Humans Hypnotics and Sedatives/metabolism Kinetics Liver/metabolism Pharmaceutical Preparations/metabolism
Chemicals
Analgesics Anti-Anxiety Agents Anti-Arrhythmia Agents Anti-Infective Agents Hypnotics and Sedatives Pharmaceutical Preparations Ethanol
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lane E A
Guthrie S
Linnoila M
References (88)
88 references, click to expand
  1. Ethanol-induced increase in procainamide acetylation in man.
    Br J Clin Pharmacol. 1982 Feb;13(2):203-8 PMID: 7059417
  2. Effects of acute alcohol administration on propranolol absorption.
    Int J Clin Pharmacol Ther Toxicol. 1980 Jul;18(7):317-9 PMID: 7429677
  3. Effect of ethanol intake on disopyramide elimination by healthy volunteers.
    Eur J Clin Pharmacol. 1983;25(1):103-5 PMID: 6617710
  4. Genetic and environmental factors affecting ethanol metabolism in man.
    Clin Pharmacol Ther. 1971 Mar-Apr;12(2):192-201 PMID: 5102974
  5. Ethanol and gastric function.
    Gastroenterology. 1972 Mar;62(3):501-2 PMID: 5011539
  6. THE ACETYLATION OF ISONIAZID IN ALCOHOLICS.
    Q J Stud Alcohol. 1964 Sep;25:541-3 PMID: 14211150
  7. Inhibition of drug metabolism by acute ethanol intoxication. A hepatic microsomal mechanism.
    Am J Med. 1970 Dec;49(6):801-6 PMID: 5006618
  8. Fatal chlormethiazole poisoning in chronic alcoholics.
    Br Med J. 1977 Sep 3;2(6087):614 PMID: 902004
  9. Diazepam actions and plasma concentrations following ethanol ingestion.
    Eur J Clin Pharmacol. 1977;11(5):345-9 PMID: 880973
  10. Mechanism of the effect of acute ethanol on hexobarbital metabolism.
    Biochem Pharmacol. 1976 Jul 15;25(14):1613-6 PMID: 942461
  11. Effect of alcoholic beverages on the pharmacokinetics of doxycycline in man.
    Acta Pharmacol Toxicol (Copenh). 1982 May;50(5):370-3 PMID: 7113712
  12. Toxicological investigations of six chlormethiazole-related deaths.
    Forensic Sci Int. 1979 Jul-Aug;14(1):49-55 PMID: 468085
  13. Increased rate of tolbutamide metabolism in alcoholic patients.
    JAMA. 1969 Jan 13;207(2):363-5 PMID: 5818164
  14. Factors affecting drug metabolism.
    Ann N Y Acad Sci. 1971 Jul 6;179:43-66 PMID: 4398309
  15. Metabolite to parent drug concentration ratio as a function of parent drug extraction ratio: cases of nonportal route of administration.
    J Pharmacokinet Biopharm. 1981 Aug;9(4):489-96 PMID: 7310646
  16. [In vivo drug release from microencapsulated acetylsalicylic acid with simultaneous alcohol uptake].
    Arzneimittelforschung. 1980;30(5):836-9 PMID: 7190431
  17. [Pharmacokinetic studies on absorption and excretion of oxazepam in Combination with alcohol (author's transl)].
    Arzneimittelforschung. 1975 Nov;25(11):1840-5 PMID: 1106447
  18. Drug interactions with alcohol.
    Drugs. 1979 Oct;18(4):299-311 PMID: 387374
  19. Alcoholism, alcohol, and drugs.
    Science. 1971 Jun 11;172(3988):1097-102 PMID: 5574515
  20. The effect of ethanol on residual plasma methaqualone concentrations and behaviour in volunteers who have taken Mandrax.
    Br J Clin Pharmacol. 1977 Apr;4(2):245-7 PMID: 861141
  21. Prevention of acetaminophen-induced hepatotoxicity by acute ethanol administration in the rat: comparison with carbon tetrachloride-induced hepatoxicity.
    J Pharmacol Exp Ther. 1981 Sep;218(3):805-10 PMID: 7264962
  22. Effect of plasma protein and tissue binding on the biologic half-life of drugs.
    Clin Pharmacol Ther. 1978 Jul;24(1):1-4 PMID: 657710
  23. Alcohol, amino acids, and albumin synthesis.
    Gastroenterology. 1974 Dec;67(6):1200-13 PMID: 4430433
  24. Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man.
    Int J Clin Pharmacol Biopharm. 1976 Dec;14(4):303-7 PMID: 1002368
  25. Metabolism of trichloroethylene in man. III. Interaction of trichloroethylene and ethanol.
    Arch Toxicol. 1975;33(3):173-89 PMID: 1173750
  26. Influence of alcohol on the pharmacokinetics of diazepam controlled-release formulation in healthy volunteers.
    J Clin Pharmacol. 1982 Nov-Dec;22(11-12):557-61 PMID: 7161409
  27. THE EFFECT OF ETHANOL UPON SYSTEMIC AND HEPATIC BLOOD FLOW IN MAN.
    Am J Clin Nutr. 1963 Aug;13:68-74 PMID: 14051216
  28. Diazepam kinetics in acute alcohol withdrawal.
    Clin Pharmacol Ther. 1979 Jun;25(6):832-6 PMID: 445950
  29. Differences in the potentiation of carbon tetrachloride in rats by ethanol and isopropanol pretreatment.
    Toxicol Appl Pharmacol. 1971 Sep;20(1):105-12 PMID: 4329357
  30. Isoniazid-related hepatitis: a U.S. Public Health Service cooperative surveillance study.
    Am Rev Respir Dis. 1978 Jun;117(6):991-1001 PMID: 666111
  31. Differential effects of benzodiazepine disposition by disulfiram and ethanol.
    Arzneimittelforschung. 1980;30(5a):882-6 PMID: 6106489
  32. Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction.
    Eur J Clin Pharmacol. 1983;25(3):325-31 PMID: 6628520
  33. Analysis of parent drug-metabolite relationship in the presence of an inducer. Application to the carbamazepine-clobazam interaction in normal man.
    Drug Metab Dispos. 1983 Jul-Aug;11(4):286-92 PMID: 6137332
  34. Mechanism of the preventive effect of ethanol on acetaminophen-induced hepatoxicity.
    J Pharmacol Exp Ther. 1981 Sep;218(3):811-5 PMID: 7264963
  35. Imipramine disposition in alcoholics.
    J Clin Psychopharmacol. 1982 Feb;2(1):2-7 PMID: 7068940
  36. Ethanol and antipyrine clearance.
    Clin Pharmacol Ther. 1981 Jul;30(1):101-4 PMID: 7237890
  37. Induction and inhibition of hepatic microsomal and mitochondrial enzymes by ethanol.
    Lab Invest. 1970 Jun;22(6):569-80 PMID: 5430804
  38. Liver parenchymal cell injury. IV. Pattern of incorporation of carbon and chlorine from carbon tetrachloride into chemical constituents of liver in vivo.
    J Pharmacol Exp Ther. 1967 Jan;155(1):117-26 PMID: 6017333
  39. Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations.
    J Pharm Sci. 1973 Nov;62(11):1789-96 PMID: 4758075
  40. Triazolam and ethanol interaction: kinetic and dynamic consequences.
    Clin Pharmacol Ther. 1985 May;37(5):558-62 PMID: 2859136
  41. Effect of a cocktail on diazepam absorption.
    Psychopharmacology (Berl). 1978 Apr 28;57(2):199-203 PMID: 418454
  42. Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics.
    Clin Pharmacol Ther. 1981 Sep;30(3):390-7 PMID: 7273603
  43. Ethanol-induced increase in drug acetylation in man and isolated rat liver cells.
    Br Med J. 1978 Nov 4;2(6147):1260-2 PMID: 709306
  44. Hepatic vein oxygenation, liver blood flow, and the rate of ethanol metabolism in recently abstinent alcoholic patients.
    Eur J Clin Invest. 1980 Jun;10(3):211-8 PMID: 6783417
  45. Apparent potentiation of acetaminophen hepatotoxicity by alcohol.
    Ann Intern Med. 1980 Apr;92(4):511 PMID: 7362155
  46. The effect of mild alcohol consumption on the metabolism of acetaminophen in man.
    Res Commun Chem Pathol Pharmacol. 1982 Oct;38(1):57-70 PMID: 7146622
  47. Disposition of methadone in man after a single oral dose.
    Clin Pharmacol Ther. 1972 Nov-Dec;13(6):923-30 PMID: 5081605
  48. Commentary: a physiological approach to hepatic drug clearance.
    Clin Pharmacol Ther. 1975 Oct;18(4):377-90 PMID: 1164821
  49. Effect of carbon tetrachloride on the nervous system.
    AMA Arch Neurol Psychiatry. 1953 Nov;70(5):635-49 PMID: 13091512
  50. Ethanol and oral diazepam absorption.
    N Engl J Med. 1977 Jan 27;296(4):186-9 PMID: 831088
  51. Alcohol-chlorpromazine interaction in psychiatric patients.
    Agressologie. 1972;13(1):67-74 PMID: 5073656
  52. Effect of alcohol on propylthiouracil disposition.
    Clin Pharmacol Ther. 1983 May;33(5):663-7 PMID: 6839636
  53. Human and animal study on elimination from plasma and metabolism of diazepam after chronic alcohol intake.
    Acta Pharmacol Toxicol (Copenh). 1975 Jan;36(1):33-8 PMID: 1173721
  54. Effects of plasma protein binding of drugs on duration and intensity of pharmacological activity.
    J Pharm Sci. 1976 Aug;65(8):1264-5 PMID: 978453
  55. Interaction of chloral hydrate and ethanol in man. I. Metabolism.
    Clin Pharmacol Ther. 1972 Jan-Feb;13(1):37-49 PMID: 4550322
  56. Hepatic microsomal enzymes in man and rat: induction and inhibition by ethanol.
    Science. 1968 Nov 8;162(3854):690-1 PMID: 5687818
  57. THE ACTION OF CARBON TETRACHLORIDE ON THE LIVER.
    Br Med J. 1922 Nov 11;2(3228):907-8 PMID: 20770915
  58. Alcohol does not enhance diazepam absorption.
    Pharmacology. 1981;22(4):263-8 PMID: 7267697
  59. Short-term ethanol administration impairs the elimination of chlordiazepoxide (Librium) in man.
    Eur J Clin Pharmacol. 1980 Oct;18(3):275-8 PMID: 7439248
  60. Clearance concepts in pharmacokinetics.
    J Pharmacokinet Biopharm. 1973 Apr;1(2):123-36 PMID: 4764426
  61. Comparison of blood clearance of ethanol and tolbutamide and the activity of hepatic ethanol-oxidizing and drug-metabolizing enzymes in chronic alcoholic subjects.
    Am J Clin Nutr. 1972 Feb;25(2):135-9 PMID: 5009780
  62. Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydranize metabolites.
    Clin Pharmacol Ther. 1975 Jul;18(1):70-9 PMID: 1149365
  63. Increased rate of clearance of drugs from the circulation of alcoholics.
    Am J Med Sci. 1969 Jul;258(1):35-9 PMID: 4894493
  64. Rationale for monitoring free drug levels.
    Clin Pharmacokinet. 1984 Jan;9 Suppl 1:1-9 PMID: 6705421
  65. Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats.
    Am J Med. 1971 Sep;51(3):346-51 PMID: 5115992
  66. Drug interactions: the effects of alcohol and meprobamate applied singly and jointly in human subjects. IV. The concentrations of alcohol and meprobamate in the blood.
    J Stud Alcohol Suppl. 1975 Nov;7:162-76 PMID: 1186259
  67. Clinical pharmacokinetics of hypnotics.
    Clin Pharmacokinet. 1977 Mar-Apr;2(2):93-109 PMID: 16715
  68. Interaction of ethanol oxidation with glucuronidation in isolated hepatocytes.
    Biochem Pharmacol. 1978;27(22):2583-8 PMID: 215162
  69. Intravenous diazepam and oral ethanol interaction.
    Clin Pharmacol Ther. 1980 Nov;28(5):638-45 PMID: 7438683
  70. Interaction of methadone and ethanol metabolism.
    J Pharmacol Exp Ther. 1978 Oct;207(1):123-9 PMID: 702334
  71. The effect of a single dose of ethanol on pharmacokinetics of paracetamol.
    Pol J Pharmacol Pharm. 1978 Nov-Dec;30(6):749-53 PMID: 755241
  72. Drug interactions with isoniazid metabolism in rats.
    J Pharm Sci. 1977 Sep;66(9):1322-6 PMID: 903875
  73. Increased carbon tetrachloride hepatotoxicity, and its mechanism, after chronic ethanol consumption.
    Gastroenterology. 1974 Mar;66(3):415-22 PMID: 4149842
  74. Drug kinetics and alcohol ingestion.
    Clin Pharmacokinet. 1978 Nov-Dec;3(6):440-52 PMID: 31257
  75. Potentiation of carbon tetrachloride toxicity by aliphatic alcohols.
    Arch Environ Health. 1967 Mar;14(3):447-9 PMID: 4951677
  76. Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment.
    Arch Intern Med. 1981 Feb 23;141(3 Spec No):380-5 PMID: 7469629
  77. Effect of short-term ethanol administration on lorazepam clearance.
    Hepatology. 1981 Jan-Feb;1(1):47-53 PMID: 6116659
  78. Effect of ethanol on the pharmacokinetics of 2-14C-methaqualone in the rat.
    Life Sci. 1977 Jun 1;20(11):1871-8 PMID: 875625
  79. Kinetic and dynamic interaction of clobazam and alcohol.
    Br J Clin Pharmacol. 1979;7 Suppl 1:91S-97S PMID: 35214
  80. Chlorpromazine inhibition of ethanol metabolism without prevention of fatty liver.
    Biochem Med. 1972 Feb;6(1):77-81 PMID: 5023890
  81. [Pharmacokinetic studies on interactions between dipotassium clorazepate and alcohol after oral application (author's transl)].
    Arzneimittelforschung. 1978;28(7):1187-91 PMID: 39573
  82. Alcohol-drugs interaction in man: alcohol and tolbutamide.
    Eur J Clin Invest. 1971 Sep;1(6):421-4 PMID: 5121732
  83. Correlation of alcohol and tolbutamide blood clearance rates with microsomal alcohol-metabolizing enzyme activity.
    Am J Clin Nutr. 1973 Feb;26(2):161-4 PMID: 4145020
  84. Serum chlordiazepoxide, diazepam and thioridazine concentrations after the simultaneous ingestion of alcohol or placebo drink.
    Ann Clin Res. 1974 Feb;6(1):4-6 PMID: 4595066
  85. Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide.
    Br J Clin Pharmacol. 1979 Jan;7(1):95-100 PMID: 760747
  86. Apparent volumes of distribution and drug binding to plasma proteins and tissues.
    Eur J Clin Pharmacol. 1978 Jul 30;13(5):373-80 PMID: 668796
  87. Diazepam pharmacokinetics after intravenous administration in alcohol withdrawal.
    Br J Clin Pharmacol. 1983 Jan;15(1):125-7 PMID: 6849737
  88. Plasma protein binding of diazepam and tolbutamide in chronic alcoholics.
    J Clin Pharmacol. 1976 Jul;16(7):345-51 PMID: 947967
Article Info
Journal
Clinical pharmacokinetics
Abbr.
Clin Pharmacokinet
ISSN
0312-5963
DOI
10.2165/00003088-198510030-00003
Published
1985-00-00
Pages
228-47
Language
English
Region
Switzerland
NLM ID
7606849
Subset
IM
External Links
PubMed source DOI: 10.2165/00003088-198510030-00003 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2