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Pharmacokinetic and Pharmacodynamic Drug Interactions with Ethanol (Alcohol)

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Abstract

Ethanol (alcohol) is one of the most widely used legal drugs in the world. Ethanol is metabolized by alcohol dehydrogenase (ADH) and the cytochrome P450 (CYP) 2E1 drug-metabolizing enzyme that is also responsible for the biotransformation of xenobiotics and fatty acids. Drugs that inhibit ADH or CYP2E1 are the most likely theoretical compounds that would lead to a clinically significant pharmacokinetic interaction with ethanol, which include only a limited number of drugs. Acute ethanol primarily alters the pharmacokinetics of other drugs by changing the rate and extent of absorption, with more limited effects on clearance. Both acute and chronic ethanol use can cause transient changes to many physiologic responses in different organ systems such as hypotension and impairment of motor and cognitive functions, resulting in both pharmacokinetic and pharmacodynamic interactions. Evaluating drug interactions with long-term use of ethanol is uniquely challenging. Specifically, it is difficult to distinguish between the effects of long-term ethanol use on liver pathology and chronic malnutrition. Ethanol-induced liver disease results in decreased activity of hepatic metabolic enzymes and changes in protein binding. Clinical studies that include patients with chronic alcohol use may be evaluating the effects of mild cirrhosis on liver metabolism, and not just ethanol itself. The definition of chronic alcohol use is very inconsistent, which greatly affects the quality of the data and clinical application of the results. Our study of the literature has shown that a significantly higher volume of clinical studies have focused on the pharmacokinetic interactions of ethanol and other drugs. The data on pharmacodynamic interactions are more limited and future research addressing pharmacodynamic interactions with ethanol, especially regarding the non-central nervous system effects, is much needed.

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References

  1. Substance Abuse & Mental Health Services Administration (SAMHSA). National Survey on Drug Use and Health (NSDUH). 2012. http://who.int/substance_abuse/publications/global_alcohol_report/msb_gsr_2014_2.pdf?ua=1. Accessed 25 May 2014.

  2. The World Health Organization. Global status report on alcohol and health. 2014. http://who.int/substance_abuse/publications/global_alcohol_report/msb_gsr_2014_2.pdf?ua=1. Accessed 25 May 2014.

  3. Centers for Disease Control and Prevention. http://www.cdc.gov/alcohol/data-stats.htm. Accessed 25 May 2014.

  4. Norberg A, Jones AW, Hahn RG, et al. Role of variability in explaining ethanol pharmacokinetics: research and forensic applications. Clin Pharmacokinet. 2003;42(1):1–31.

    CAS  PubMed  Google Scholar 

  5. Cederbaum AI. Alcohol metabolism. Clin Liver Dis. 2012;16(4):667–85.

    PubMed Central  PubMed  Google Scholar 

  6. Salaspuro MP, Lindros KO, Pikkarainen PH. Effect of 4-methylpyrazole on ethanol elimination rate and hepatic redox changes in alcoholics with adequate or inadequate nutrition and in nonalcoholic controls. Metabolism. 1978;27(6):631–9.

    CAS  PubMed  Google Scholar 

  7. Matsumoto H, Fukui Y. Pharmacokinetics of ethanol: a review of the methodology. Addict Biol. 2002;7(1):5–14.

    CAS  PubMed  Google Scholar 

  8. Shankar K, Ronis MJ, Badger TM. Effects of pregnancy and nutritional status on alcohol metabolism. Alcohol Res Health. 2007;30(1):55–9.

    PubMed Central  PubMed  Google Scholar 

  9. Riveros-Rosas H, Julian-Sanchez A, Pina E. Enzymology of ethanol and acetaldehyde metabolism in mammals. Arch Med Res. 1997;28(4):453–71.

    CAS  PubMed  Google Scholar 

  10. Edenberg HJ. The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants. Alcohol Res Health. 2007;30(1):5–13.

    PubMed Central  PubMed  Google Scholar 

  11. Crabb DW, Matsumoto M, Chang D, et al. Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc. 2004;63(1):49–63.

    CAS  PubMed  Google Scholar 

  12. Lieber CS. Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev. 1997;77(2):517–44.

    CAS  PubMed  Google Scholar 

  13. Caro AA, Cederbaum AI. Oxidative stress, toxicology, and pharmacology of CYP2E1. Annu Rev Pharmacol Toxicol. 2004;44:27–42.

    CAS  PubMed  Google Scholar 

  14. Aubert J, Begriche K, Knockaert L, et al. Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: mechanisms and pathophysiological role. Clin Res Hepatol Gastroenterol. 2011;35(10):630–7.

    CAS  PubMed  Google Scholar 

  15. Ahn CY, Bae SK, Jung YS, et al. Pharmacokinetic parameters of chlorzoxazone and its main metabolite, 6-hydroxychlorzoxazone, after intravenous and oral administration of chlorzoxazone to liver cirrhotic rats with diabetes mellitus. Drug Metab Dispos. 2008;36(7):1233–41.

    CAS  PubMed  Google Scholar 

  16. Lucas D, Farez C, Bardou LG, et al. Cytochrome P450 2E1 activity in diabetic and obese patients as assessed by chlorzoxazone hydroxylation. Fundam Clin Pharmacol. 1998;12(5):553–8.

    CAS  PubMed  Google Scholar 

  17. Brown BL, Allis JW, Simmons JE, et al. Fasting for less than 24 h induces cytochrome P450 2E1 and 2B1/2 activities in rats. Toxicol Lett. 1995;81(1):39–44.

    CAS  PubMed  Google Scholar 

  18. O’Shea D, Davis SN, Kim RB, et al. Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: a putative probe of CYP2E1 activity. Clin Pharmacol Ther. 1994;56(4):359–67.

    PubMed  Google Scholar 

  19. McGehee RE Jr, Ronis MJ, Cowherd RM, et al. Characterization of cytochrome P450 2E1 induction in a rat hepatoma FGC-4 cell model by ethanol. Biochem Pharmacol. 1994;48(9):1823–33.

    CAS  PubMed  Google Scholar 

  20. Koop DR, Tierney DJ. Multiple mechanisms in the regulation of ethanol-inducible cytochrome P450IIE1. BioEssays 1990;12(9):429–35.

    CAS  PubMed  Google Scholar 

  21. Ferreira MP, Weems MK. Alcohol consumption by aging adults in the United States: health benefits and detriments. J Am Diet Assoc. 2008;108(10):1668–76.

    PubMed  Google Scholar 

  22. Seidl S, Wurst FM, Alt A. Ethyl glucuronide-a biological marker for recent alcohol consumption. Addict Biol. 2001;6(3):205–12.

    CAS  PubMed  Google Scholar 

  23. Frezza M, di Padova C, Pozzato G, et al. High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med. 1990;322(2):95–9.

    CAS  PubMed  Google Scholar 

  24. Baraona E, Abittan CS, Dohmen K, et al. Gender differences in pharmacokinetics of alcohol. Alcohol Clin Exp Res. 2001;25(4):502–7.

    CAS  PubMed  Google Scholar 

  25. Correa CL, Oga S. Effects of the menstrual cycle of white women on ethanol toxicokinetics. J Stud Alcohol. 2004;65(2):227–31.

    PubMed  Google Scholar 

  26. Lucey MR, Hill EM, Young JP, et al. The influences of age and gender on blood ethanol concentrations in healthy humans. J Stud Alcohol. 1999;60(1):103–10.

    CAS  PubMed  Google Scholar 

  27. Cigarroa RG, Lange RA, Popma JJ, et al. Ethanol-induced coronary vasodilation in patients with and without coronary artery disease. Am Heart J. 1990;119(2 Pt 1):254–9.

    CAS  PubMed  Google Scholar 

  28. Gazzieri D, Trevisani M, Tarantini F, et al. Ethanol dilates coronary arteries and increases coronary flow via transient receptor potential vanilloid 1 and calcitonin gene-related peptide. Cardiovasc Res. 2006;70(3):589–99.

    CAS  PubMed  Google Scholar 

  29. Marchi KC, Muniz JJ, Tirapelli CR. Hypertension and chronic ethanol consumption: what do we know after a century of study? World J Cardiol. 2014;6(5):283–94.

    PubMed Central  PubMed  Google Scholar 

  30. Rossinen J, Sinisalo J, Partanen J, et al. Effects of acute alcohol infusion on duration and dispersion of QT interval in male patients with coronary artery disease and in healthy controls. Clin Cardiol. 1999;22(9):591–4.

    CAS  PubMed  Google Scholar 

  31. Thomas AP, Rozanski DJ, Renard DC, et al. Effects of ethanol on the contractile function of the heart: a review. Alcohol Clin Exp Res. 1994;18(1):121–31.

    CAS  PubMed  Google Scholar 

  32. Greenspon AJ, Schaal SF. The “holiday heart”: electrophysiologic studies of alcohol effects in alcoholics. Ann Intern Med. 1983;98(2):135–9.

    CAS  PubMed  Google Scholar 

  33. Sengul C, Cevik C, Ozveren O, et al. Acute alcohol consumption is associated with increased interatrial electromechanical delay in healthy men. Cardiol J. 2011;18(6):682–6.

    PubMed  Google Scholar 

  34. Sano F, Ohira T, Kitamura A, et al. Heavy alcohol consumption and risk of atrial fibrillation. The Circulatory Risk in Communities Study (CIRCS). Circ J. 2014;78(4):955–61.

    PubMed  Google Scholar 

  35. Ghahramani P, Ellis SW, Lennard MS, et al. Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997;43(2):137–44.

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Scott DB, Fagan D, Tiplady B. Effects of amitriptyline and zimelidine in combination with ethanol. Psychopharmacology (Berl). 1982;76(3):209–11.

    CAS  PubMed  Google Scholar 

  37. Warrington SJ, Ankier SI, Turner P. An evaluation of possible interactions between ethanol and trazodone or amitriptyline. Br J Clin Pharmacol. 1984;18(4):549–57.

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Dorian P, Sellers EM, Reed KL, et al. Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction. Eur J Clin Pharmacol. 1983;25(3):325–31.

    CAS  PubMed  Google Scholar 

  39. Allen D, Lader M. Interactions of alcohol with amitriptyline, fluoxetine and placebo in normal subjects. Int Clin Psychopharmacol. 1989;4(Suppl 1):7–14.

    PubMed  Google Scholar 

  40. Linnoila M, Johnson J, Dubyoski K, et al. Effects of antidepressants on skilled performance. Br J Clin Pharmacol. 1984;18(Suppl 1):109S–20S.

    PubMed Central  PubMed  Google Scholar 

  41. Seppala T, Stromberg C, Bergman I. Effects of zimeldine, mianserin and amitriptyline on psychomotor skills and their interaction with ethanol a placebo controlled cross-over study. Eur J Clin Pharmacol. 1984;27(2):181–9.

    CAS  PubMed  Google Scholar 

  42. Faucette SR, Hawke RL, Lecluyse EL, et al. Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. Drug Metab Dispos. 2000;28(10):1222–30.

    CAS  PubMed  Google Scholar 

  43. Posner J, Bye A, Jeal S, et al. Alcohol and bupropion pharmacokinetics in healthy male volunteers. Eur J Clin Pharmacol. 1984;26(5):627–30.

    CAS  PubMed  Google Scholar 

  44. Miura M, Ohkubo T. Identification of human cytochrome P450 enzymes involved in the major metabolic pathway of fluvoxamine. Xenobiotica. 2007;37(2):169–79.

    CAS  PubMed  Google Scholar 

  45. Jeppesen U, Gram LF, Vistisen K, et al. Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine. Eur J Clin Pharmacol. 1996;51(1):73–8.

    CAS  PubMed  Google Scholar 

  46. Spigset O, Carleborg L, Hedenmalm K, et al. Effect of cigarette smoking on fluvoxamine pharmacokinetics in humans. Clin Pharmacol Ther. 1995;58(4):399–403.

    CAS  PubMed  Google Scholar 

  47. van Harten J, Stevens LA, Raghoebar M, et al. Fluvoxamine does not interact with alcohol or potentiate alcohol-related impairment of cognitive function. Clin Pharmacol Ther. 1992;52(4):427–35.

    PubMed  Google Scholar 

  48. Linnoila M, Stapleton JM, George DT, et al. Effects of fluvoxamine, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers. J Clin Psychopharmacol. 1993;13(3):175–80.

    CAS  PubMed  Google Scholar 

  49. Otton SV, Ball SE, Cheung SW, et al. Venlafaxine oxidation in vitro is catalysed by CYP2D6. Br J Clin Pharmacol. 1996;41(2):149–56.

    CAS  PubMed  Google Scholar 

  50. Lindh JD, Annas A, Meurling L, et al. Effect of ketoconazole on venlafaxine plasma concentrations in extensive and poor metabolisers of debrisoquine. Eur J Clin Pharmacol. 2003;59(5–6):401–6.

    CAS  PubMed  Google Scholar 

  51. Troy SM, Turner MB, Unruh M, et al. Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction between venlafaxine and ethanol. J Clin Pharmacol. 1997;37(11):1073–81.

    CAS  PubMed  Google Scholar 

  52. Kerr BM, Thummel KE, Wurden CJ, et al. Human liver carbamazepine: role of CYP3A4 and CYP2A8 in 10,11 epoxide formation. Biochem Pharmacol. 1994;47:1969–79.

    CAS  PubMed  Google Scholar 

  53. Sternebring B, Liden A, Andersson K, et al. Carbamazepine kinetics and adverse effects during and after ethanol exposure in alcoholics and in healthy volunteers. Eur J Clin Pharmacol. 1992;43(4):393–7.

    CAS  PubMed  Google Scholar 

  54. Tompson DJ, Crean CS. Clinical pharmacokinetics of retigabine/ezogabine. Curr Clin Pharmacol. 2013;8(4):319–31.

    CAS  PubMed  Google Scholar 

  55. Crean CS, Tompson DJ. The effects of ethanol on the pharmacokinetics, pharmacodynamics, safety, and tolerability of ezogabine (retigabine). Clin Ther. 2013;35(1):87–93.

    CAS  PubMed  Google Scholar 

  56. Blum RA, Comstock TJ, Sica DA, et al. Pharmacokinetics of gabapentin in subjects with various degrees of renal function. Clin Pharmacol Ther. 1994;56:154–9.

    CAS  PubMed  Google Scholar 

  57. Bisaga A, Evans SM. The acute effects of gabapentin in combination with alcohol in heavy drinkers. Drug Alcohol Depend. 2006;83(1):25–32.

    CAS  PubMed  Google Scholar 

  58. Bajpai M, Roskos LK, Shen DD, et al. Roles of cytochrome P4502C9 and cytochrome P4502C19 in the stereoselective metabolism of phenytoin to its major metabolites. Drug Metab Dispos. 1996;24:1401–3.

    CAS  PubMed  Google Scholar 

  59. Sandor P, Sellers EM, Dumbrell M, et al. Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics. Clin Pharmacol Ther. 1981;30(3):390–7.

    CAS  PubMed  Google Scholar 

  60. Kater RM, Roggin G, Tobon F, et al. Increased rate of clearance of drugs from the circulation of alcoholics. Am J Med Sci. 1969;258(1):35–9.

    CAS  PubMed  Google Scholar 

  61. Frye RF, Zgheib NK, Matzke GR, et al. Liver disease selectively modulates cytochrome P450–mediated metabolism. Clin Pharmacol Ther. 2006;80(3):235–45.

    CAS  PubMed  Google Scholar 

  62. Maxwell HG, Dubois S, Weaver B, et al. The additive effects of alcohol and benzodiazepines on driving. Can J Public Health. 2010;101(5):353–7.

    PubMed  Google Scholar 

  63. Thomas RE. Benzodiazepine use and motor vehicle accidents. Systematic review of reported association. Can Fam Physician. 1998;44:799–808.

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Orriols L, Philip P, Moore N, et al. Benzodiazepine-like hypnotics and the associated risk of road traffic accidents. Clin Pharmacol Ther. 2011;89(4):595–601.

    CAS  PubMed  Google Scholar 

  65. Linnoila M. Effects of diazepam, chlordiazepoxide, thioridazine, haloperidole, flupenthixole and alcohol on psychomotor skills related to driving. Ann Med Exp Biol Fenn. 1973;51(3):125–32.

    CAS  PubMed  Google Scholar 

  66. Eves FF, Lader MH. The effects of alcohol on psychological functions in normal volunteers after 8 days’ treatment with pipequaline (PK 8165), diazepam or placebo. Eur J Clin Pharmacol. 1989;36(1):47–52.

    CAS  PubMed  Google Scholar 

  67. Willumeit HP, Ott H, Neubert W, et al. Alcohol interaction of lormetazepam, mepindolol sulphate and diazepam measured by performance on the driving simulator. Pharmacopsychiatry. 1984;17(2):36–43.

    CAS  PubMed  Google Scholar 

  68. Seppala T, Aranko K, Mattila MJ, et al. Effects of alcohol on buspirone and lorazepam actions. Clin Pharmacol Ther. 1982;32(2):201–7.

    CAS  PubMed  Google Scholar 

  69. Willumeit HP, Ott H, Neubert W. Simulated car driving as a useful technique for the determination of residual effects and alcohol interaction after short- and long-acting benzodiazepines. Psychopharmacology. 1984;1(Suppl):182–92.

    CAS  PubMed  Google Scholar 

  70. Sellers EM, Busto U. Benzodiazepines and ethanol: assessment of the effects and consequences of psychotropic drug interactions. J Clin Psychopharmacol. 1982;2(4):249–62.

    CAS  PubMed  Google Scholar 

  71. Andersson T, Miners JO, Veronese ME, et al. Diazepam metabolism by human liver microsomes is mediated by both S-mephenytoin hydroxylase and CYP3A isoforms. Br J Clin Pharmacol. 1994;38:131–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Sellers EM, Naranjo CA, Giles HG, et al. Intravenous diazepam and oral ethanol interaction. Clin Pharmacol Ther. 1980;28(5):638–45.

    CAS  PubMed  Google Scholar 

  73. Hayes SL, Pablo G, Radomski T, et al. Ethanol and oral diazepam absorption. N Engl J Med. 1977;296(4):186–9.

    CAS  PubMed  Google Scholar 

  74. Erwin CW, Linnoila M, Hartwell J, et al. Effects of buspirone and diazepam, alone and in combination with alcohol, on skilled performance and evoked potentials. J Clin Psychopharmacol. 1986;6(4):199–209.

    CAS  PubMed  Google Scholar 

  75. van Steveninck AL, Gieschke R, Schoemaker RC, et al. Pharmacokinetic and pharmacodynamic interactions of bretazenil and diazepam with alcohol. Br J Clin Pharmacol. 1996;41(6):565–73.

    PubMed  Google Scholar 

  76. Giraud C, Tran A, Rey E, et al. In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004;32(11):1279–86.

    CAS  PubMed  Google Scholar 

  77. Taeuber K, Badian M, Brettel HF, et al. Kinetic and dynamic interaction of clobazam and alcohol. Br J Clin Pharmacol. 1979;7(Suppl 1):91S–7S.

    PubMed Central  PubMed  Google Scholar 

  78. Uchaipichat V, Suthisisang C, Miners JO. The glucuronidation of R- and S-lorazepam: human liver microsomal kinetics, UDP-glucuronosyltransferase enzyme selectivity, and inhibition by drugs. Drug Metab Dispos. 2013;41(6):1273–84.

    CAS  PubMed  Google Scholar 

  79. Hoyumpa AM, Patwardhan R, Maples M, et al. Effect of short-term ethanol administration on lorazepam clearance. Hepatology. 1981;1(1):47–53.

    CAS  PubMed  Google Scholar 

  80. Soo-ampon S, Wongwitdecha N, Plasen S, et al. Effects of word frequency on recall memory following lorazepam, alcohol, and lorazepam alcohol interaction in healthy volunteers. Psychopharmacology (Berl). 2004;176(3–4):420–5.

    CAS  PubMed  Google Scholar 

  81. Whiting B, Lawrence JR, Skellern GG, et al. Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide. Br J Clin Pharmacol. 1979;7(1):95–100.

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Perry PJ, Wilding DC, Fowler RC, et al. Absorption of oral intramuscular chlordiazepoxide by alcoholics. Clin Pharmacol Ther. 1978;23(5):535–41.

    CAS  PubMed  Google Scholar 

  83. Sellers EM, Greenblatt DJ, Zilm DH, et al. Decline in chlordiazepoxide plasma levels during fixed-dose therapy of alcohol withdrawal. Br J Clin Pharmacol. 1978;6(4):370–2.

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Sellman R, Kanto J, Raijola E, et al. Human and animal study on elimination from plasma and metabolism of diazepam after chronic alcohol intake. Acta Pharmacol Toxicol (Copenh). 1975;36(1):33–8.

    CAS  PubMed  Google Scholar 

  85. Sellman R, Pekkarinen A, Kangas L, et al. Reduced concentrations of plasma diazepam in chronic alcoholic patients following an oral administration of diazepam. Acta Pharmacol Toxicol (Copenh). 1975;36(1):25–32.

    CAS  PubMed  Google Scholar 

  86. Gudin JA, Mogali S, Jones JD, et al. Risks, management, and monitoring of combination opioid, benzodiazepines, and/or alcohol use. Postgrad Med. 2013;125(4):115–30.

    PubMed Central  PubMed  Google Scholar 

  87. Ali NA, Marshall RW, Allen EM, et al. Comparison of the effects of therapeutic doses of meptazinol and a dextropropoxyphene/paracetamol mixture alone and in combination with ethanol on ventilatory function and saccadic eye movements. Br J Clin Pharmacol. 1985;20(6):631–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Johnson F, Wagner G, Sun S, et al. Effect of concomitant ingestion of alcohol on the in vivo pharmacokinetics of KADIAN (morphine sulfate extended-release) capsules. J Pain. 2008;9(4):330–6.

    CAS  PubMed  Google Scholar 

  89. Sokolowska M, Sun S, Johnson F, et al. The effect of morphine in combination with ethanol on safety, pharmacodynamics, and pharmacokinetic measures in healthy volunteers [abstract]. J Pain. 2007;8:S39.

    Google Scholar 

  90. Court MH, Krishnaswamy S, Hao Q, et al. Evaluation of 3′-azido-3′-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism. Drug Metab Dispos. 2003;31(9):1125–33.

    CAS  PubMed  Google Scholar 

  91. Lotsch J, Stockmann A, Kobal G, et al. Pharmacokinetics of morphine and its glucuronides after intravenous infusion of morphine and morphine-6-glucuronide in healthy volunteers. Clin Pharmacol Ther. 1996;60(3):316–25.

    CAS  PubMed  Google Scholar 

  92. Bodd E, Drevon CA, Kveseth N, et al. Ethanol inhibition of codeine and morphine metabolism in isolated rat hepatocytes. J Pharmacol Exp Ther. 1986;237(1):260–4.

    CAS  PubMed  Google Scholar 

  93. Bodd E, Gadeholt G, Christensson PI, et al. Mechanisms behind the inhibitory effect of ethanol on the conjugation of morphine in rat hepatocytes. J Pharmacol Exp Ther. 1986;239(3):887–90.

    CAS  PubMed  Google Scholar 

  94. Hoiseth G, Andersen JM, Morland J. Less glucuronidation of morphine in the presence of ethanol in vivo. Eur J Clin Pharmacol. 2013;69(9):1683–7.

    PubMed  Google Scholar 

  95. Portenoy RK, Foley KM, Stulman J, et al. Plasma morphine and morphine-6-glucuronide during chronic morphine therapy for cancer pain: plasma profiles, steady-state concentrations and the consequences of renal failure. Pain. 1991;47(1):13–9.

    CAS  PubMed  Google Scholar 

  96. Sjogren P, Thunedborg LP, Christrup L, et al. Is development of hyperalgesia, allodynia and myoclonus related to morphine metabolism during long-term administration? Six case histories. Acta Anaesthesiol Scand. 1998;42(9):1070–5.

    CAS  PubMed  Google Scholar 

  97. Soderberg Lofdal KC, Andersson ML, Gustafsson LL. Cytochrome P450-mediated changes in oxycodone pharmacokinetics/pharmacodynamics and their clinical implications. Drugs. 2013;73(6):533–43.

    PubMed  Google Scholar 

  98. Zacny JP, Gutierrez S. Subjective, psychomotor, and physiological effects of oxycodone alone and in combination with ethanol in healthy volunteers. Psychopharmacology (Berl). 2011;218(3):471–81.

    CAS  PubMed  Google Scholar 

  99. Girre C, Hirschhorn M, Bertaux L, et al. Enhancement of propoxyphene bioavailability by ethanol. Relation to psychomotor and cognitive function in healthy volunteers. Eur J Clin Pharmacol. 1991;41(2):147–52.

    CAS  PubMed  Google Scholar 

  100. Rush CR. Pretreatment with hydromorphone, a mu-opioid agonist, does not alter the acute behavioral and physiological effects of ethanol in humans. Alcohol Clin Exp Res. 2001;25(1):9–17.

    CAS  PubMed  Google Scholar 

  101. Markowitz JS, Patrick KS. Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder. Clin Pharmacokinet. 2001;40(10):753–72.

    CAS  PubMed  Google Scholar 

  102. Markowitz JS, Logan BK, Diamond F, et al. Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion. J Clin Psychopharmacol. 1999;19(4):362–6.

    CAS  PubMed  Google Scholar 

  103. Markowitz JS, DeVane CL, Boulton DW, et al. Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol. Drug Metab Dispos. 2000;28(6):620–4.

    CAS  PubMed  Google Scholar 

  104. Patrick KS, Straughn AB, Minhinnett RR, et al. Influence of ethanol and gender on methylphenidate pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2007;81(3):346–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  105. Koehm M, Kauert GF, Toennes SW. Influence of ethanol on the pharmacokinetics of methylphenidate’s metabolites ritalinic acid and ethylphenidate. Arzneimittelforschung. 2010;60(5):238–44.

    CAS  PubMed  Google Scholar 

  106. McEnroe JD, Fleishaker JC. Clinical pharmacokinetics of almotriptan, a serotonin 5-HT(1B/1D) receptor agonist for the treatment of migraine. Clin Pharmacokinet. 2005;44(3):237–46.

    CAS  PubMed  Google Scholar 

  107. Cabarrocas X, Salva M, Pavesi M, et al. Ethanol does not significantly affect the bioavailability of almotriptan: an open, randomized, crossover, single-dose, phase I clinical trial in healthy volunteers. Int J Clin Pharmacol Ther. 2006;44(9):443–8.

    CAS  PubMed  Google Scholar 

  108. Dorian P, Sellers EM, Kaplan HL, et al. Triazolam and ethanol interaction: kinetic and dynamic consequences. Clin Pharmacol Ther. 1985;37(5):558–62.

    CAS  PubMed  Google Scholar 

  109. Ochs HR, Greenblatt DJ, Arendt RM, et al. Pharmacokinetic noninteraction of triazolam and ethanol. J Clin Psychopharmacol. 1984;4(2):106–7.

    CAS  PubMed  Google Scholar 

  110. Kuitunen T, Mattila MJ, Seppala T. Actions and interactions of hypnotics on human performance: single doses of zopiclone, triazolam and alcohol. Int Clin Psychopharmacol. 1990;5(Suppl 2):115–30.

    PubMed  Google Scholar 

  111. Wilkinson CJ. The acute effects of zolpidem, administered alone and with alcohol, on cognitive and psychomotor function. J Clin Psychiatry. 1995;56(7):309–18.

    CAS  PubMed  Google Scholar 

  112. Roehrs T, Rosenthal L, Koshorek G, et al. Effects of zaleplon or triazolam with or without ethanol on human performance. Sleep Med. 2001;2(4):323–32.

    PubMed  Google Scholar 

  113. Chaudhuri KR, Maule S, Thomaides T, et al. Alcohol ingestion lowers supine blood pressure, causes splanchnic vasodilatation and worsens postural hypotension in primary autonomic failure. J Neurol. 1994;241(3):145–52.

    CAS  PubMed  Google Scholar 

  114. Saltiel E, Ellrodt AG, Monk JP, et al. Felodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs. 1988;36(4):387–428.

    CAS  PubMed  Google Scholar 

  115. Bailey DG, Spence JD, Edgar B, et al. Ethanol enhances the hemodynamic effects of felodipine. Clin Invest Med. 1989;12(6):357–62.

    CAS  PubMed  Google Scholar 

  116. Grundy JS, Foster RT. The nifedipine gastrointestinal therapeutic system (GITS). Evaluation of pharmaceutical, pharmacokinetic and pharmacological properties. Clin Pharmacokinet. 1996;30(1):28–51.

    CAS  PubMed  Google Scholar 

  117. Qureshi S, Laganiere S, Caille G, et al. Effect of an acute dose of alcohol on the pharmacokinetics of oral nifedipine in humans. Pharm Res. 1992;9(5):683–6.

    CAS  PubMed  Google Scholar 

  118. Tracy TS, Korzekwa KR, Gonzalez FJ, et al. Cytochrome P450 isoforms involved in metabolism of the enantiomers of verapamil and norverapamil. Br J Clin Pharmacol. 1999;47(5):545–52.

    CAS  PubMed Central  PubMed  Google Scholar 

  119. Perez-Reyes M, White WR, Hicks RE. Interaction between ethanol and calcium channel blockers in humans. Alcohol Clin Exp Res. 1992;16(4):769–75.

    CAS  PubMed  Google Scholar 

  120. Bauer LA, Schumock G, Horn J, et al. Verapamil inhibits ethanol elimination and prolongs the perception of intoxication. Clin Pharmacol Ther. 1992;52(1):6–10.

    CAS  PubMed  Google Scholar 

  121. Reidenberg MM, Drayer DE, Levy M, et al. Polymorphic acetylation procainamide in man. Clin Pharmacol Ther. 1975;17(6):722–30.

    CAS  PubMed  Google Scholar 

  122. Olsen H, Morland J. Ethanol-induced increase in procainamide acetylation in man. Br J Clin Pharmacol. 1982;13(2):203–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Nelson SD. Anagesics-Antipyretics. In: Levy RH, Thummel KE, Trager WF, Hansten PD, Eichelbaum M, editors. Metabolic drug interactions. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 447–53.

    Google Scholar 

  124. Manyike PT, Kharasch ED, Kalhorn TF, et al. Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clin Pharmacol Ther. 2000;67(3):275–82.

    CAS  PubMed  Google Scholar 

  125. Knockaert L, Descatoire V, Vadrot N, et al. Mitochondrial CYP2E1 is sufficient to mediate oxidative stress and cytotoxicity induced by ethanol and acetaminophen. Toxicol In Vitro. 2011;25(2):475–84.

    CAS  PubMed  Google Scholar 

  126. Thummel KE, Slattery JT, Nelson SD, et al. Effect of ethanol on hepatotoxicity of acetaminophen in mice and on reactive metabolite formation by mouse and human liver microsomes. Toxicol Appl Pharmacol. 1989;100(3):391–7.

    CAS  PubMed  Google Scholar 

  127. Slattery JT, Nelson SD, Thummel KE. The complex interaction between ethanol and acetaminophen. Clin Pharmacol Ther. 1996;60(3):241–6.

    CAS  PubMed  Google Scholar 

  128. Thummel KE, Slattery JT, Ro H, et al. Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults. Clin Pharmacol Ther. 2000;67(6):591–9.

    CAS  PubMed  Google Scholar 

  129. Roine R, Gentry RT, Hernandez-Munoz R, et al. Aspirin increases blood alcohol concentrations in humans after ingestion of ethanol. JAMA. 1990;264(18):2406–8.

    CAS  PubMed  Google Scholar 

  130. Truitt EB Jr, Gaynor CR, Mehl DL. Aspirin attenuation of alcohol-induced flushing and intoxication in oriental and occidental subjects. Alcohol Alcohol. 1987;1:595–9.

    Google Scholar 

  131. Gentry RT, Baraona E, Amir I, et al. Mechanism of the aspirin-induced rise in blood alcohol levels. Life Sci. 1999;65(23):2505–12.

    CAS  PubMed  Google Scholar 

  132. Melander O, Liden A, Melander A. Pharmacokinetic interactions of alcohol and acetylsalicylic acid. Eur J Clin Pharmacol. 1995;48(2):151–3.

    CAS  PubMed  Google Scholar 

  133. Kechagias S, Jonsson KA, Jones AW. Impact of gastric emptying on the pharmacokinetics of ethanol as influenced by cisapride. Br J Clin Pharmacol. 1999;48(5):728–32.

    CAS  PubMed Central  PubMed  Google Scholar 

  134. Kaufman DW, Kelly JP, Wiholm BE, et al. The risk of acute major upper gastrointestinal bleeding among users of aspirin and ibuprofen at various levels of alcohol consumption. Am J Gastroenterol. 1999;94(11):3189–96.

    CAS  PubMed  Google Scholar 

  135. Mustonen H, Kivilaakso E. Effect of luminal ethanol on epithelial resistances and cell volume in isolated necturus gastric mucosa. Dig Dis Sci. 2003;48(10):2037–44.

    CAS  PubMed  Google Scholar 

  136. Karazniewicz-Lada M, Luczak M, Glowka F. Pharmacokinetic studies of enantiomers of ibuprofen and its chiral metabolites in humans with different variants of genes coding CYP2C8 and CYP2C9 isoenzymes. Xenobiotica. 2009;39(6):476–85.

    CAS  PubMed  Google Scholar 

  137. Barron SE, Perry JR, Ferslew KE. The effect of ibuprofen on ethanol concentration and elimination rate. J Forensic Sci. 1992;37(2):432–5.

    CAS  PubMed  Google Scholar 

  138. Hernandez-Munoz R, Caballeria J, Baraona E, et al. Human gastric alcohol dehydrogenase: its inhibition by H2-receptor antagonists, and its effect on the bioavailability of ethanol. Alcohol Clin Exp Res. 1990;14(6):946–50.

    CAS  PubMed  Google Scholar 

  139. Palmer RH, Frank WO, Nambi P, et al. Effects of various concomitant medications on gastric alcohol dehydrogenase and the first-pass metabolism of ethanol. Am J Gastroenterol. 1991;86(12):1749–55.

    CAS  PubMed  Google Scholar 

  140. Gupta AM, Baraona E, Lieber CS. Significant increase of blood alcohol by cimetidine after repetitive drinking of small alcohol doses. Alcohol Clin Exp Res. 1995;19(4):1083–7.

    CAS  PubMed  Google Scholar 

  141. DiPadova C, Roine R, Frezza M, et al. Effects of ranitidine on blood alcohol levels after ethanol ingestion. Comparison with other H2-receptor antagonists. JAMA. 1992;267(1):83–6.

    CAS  PubMed  Google Scholar 

  142. Bye A, Lacey LF, Gupta S, et al. Effect of ranitidine hydrochloride (150 mg twice daily) on the pharmacokinetics of increasing doses of ethanol (0.15, 0.3, 0.6 g kg−1). Br J Clin Pharmacol. 1996;41(2):129–33.

    CAS  PubMed  Google Scholar 

  143. Amir I, Anwar N, Baraona E, et al. Ranitidine increases the bioavailability of imbibed alcohol by accelerating gastric emptying. Life Sci. 1996;58(6):511–8.

    CAS  PubMed  Google Scholar 

  144. Weinberg DS, Burnham D, Berlin JA. Effect of histamine-2 receptor antagonists on blood alcohol levels: a meta-analysis. J Gen Intern Med. 1998;13(9):594–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  145. Brown AS, James OF. Omeprazole, ranitidine, and cimetidine have no effect on peak blood ethanol concentrations, first pass metabolism or area under the time-ethanol curve under ‘real-life’ drinking conditions. Aliment Pharmacol Ther. 1998;12(2):141–5.

    CAS  PubMed  Google Scholar 

  146. Sanchez RI, Wang RW, Newton DJ, et al. Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos. 2004;32(11):1287–92.

    CAS  PubMed  Google Scholar 

  147. te Beek ET, Tatosian D, Majumdar A, et al. Placebo- and amitriptyline-controlled evaluation of central nervous system effects of the NK1 receptor antagonist aprepitant and intravenous alcohol infusion at pseudo-steady state. J Clin Pharmacol. 2013;53(8):846–56.

    Google Scholar 

  148. Zhi J, Massarella JW, Melia AT, et al. The pharmacokinetic-pharmacodynamic (digit symbol substitution test) relationship of flumazenil in a midazolam steady-state model in healthy volunteers. Clin Pharmacol Ther. 1994;56(5):530–6.

    CAS  PubMed  Google Scholar 

  149. Melia AT, Zhi J, Zelasko R, et al. The interaction of the lipase inhibitor orlistat with ethanol in healthy volunteers. Eur J Clin Pharmacol. 1998;54(9–10):773–7.

    CAS  PubMed  Google Scholar 

  150. Limdi NA, Veenstra DL. Warfarin pharmacogenetics. Pharmacotherapy. 2008;28(9):1084–97.

    CAS  PubMed Central  PubMed  Google Scholar 

  151. Havrda DE, Mai T, Chonlahan J. Enhanced antithrombotic effect of warfarin associated with low-dose alcohol consumption. Pharmacotherapy. 2005;25(2):303–7.

    PubMed  Google Scholar 

  152. Lindberg RL, Huupponen RK, Viljanen S, et al. Ethanol and the absorption of oral penicillin in man. Int J Clin Pharmacol Ther Toxicol. 1987;25(10):536–8.

    CAS  PubMed  Google Scholar 

  153. Morasso MI, Hip A, Marquez M, et al. Amoxicillin kinetics and ethanol ingestion. Int J Clin Pharmacol Ther Toxicol. 1988;26(9):428–31.

    CAS  PubMed  Google Scholar 

  154. Lassman HB, Hubbard JW, Chen BL, et al. Lack of interaction between cefpirome and alcohol. J Antimicrob Chemother. 1992;29(Suppl A):47–50.

    CAS  PubMed  Google Scholar 

  155. Kamali F. No influence of ciprofloxacin on ethanol disposition. A pharmacokinetic-pharmacodynamic interaction study. Eur J Clin Pharmacol. 1994;47(1):71–4.

    CAS  PubMed  Google Scholar 

  156. Fuhr U, Wolff T, Harder S, et al. Quinolone inhibition of cytochrome P-450-dependent caffeine metabolism in human liver microsomes. Drug Metab Dispos. 1990;18(6):1005–10.

    CAS  PubMed  Google Scholar 

  157. Watkins PB, Murray SA, Winkelman LG, et al. Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. Studies in rats and patients. J Clin Invest. 1989;83(2):688–97.

    CAS  PubMed Central  PubMed  Google Scholar 

  158. Morasso MI, Chavez J, Gai MN, et al. Influence of alcohol consumption on erythromycin ethylsuccinate kinetics. Int J Clin Pharmacol Ther Toxicol. 1990;28(10):426–9.

    CAS  PubMed  Google Scholar 

  159. Weber FH Jr, Richards RD, McCallum RW. Erythromycin: a motilin agonist and gastrointestinal prokinetic agent. Am J Gastroenterol. 1993;88(4):485–90.

    CAS  PubMed  Google Scholar 

  160. Seitz C, Garcia P, Arancibia A. Influence of ethanol ingestion on tetracycline kinetics. Int J Clin Pharmacol Ther. 1995;33(8):462–4.

    CAS  PubMed  Google Scholar 

  161. Iselius L, Evans DA. Formal genetics of isoniazid metabolism in man. Clin Pharmacokinet. 1983;8(6):541–4.

    CAS  PubMed  Google Scholar 

  162. Polasek TM, Elliot DJ, Somogyi AA, et al. An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid. Br J Clin Pharmacol. 2006;61(5):570–84.

    CAS  PubMed Central  PubMed  Google Scholar 

  163. Park KS, Sohn DH, Veech RL, et al. Translational activation of ethanol-inducible cytochrome P450 (CYP2E1) by isoniazid. Eur J Pharmacol. 1993;248(1):7–14.

    CAS  PubMed  Google Scholar 

  164. Dattani RG, Harry F, Hutchings AD, et al. The effects of acute ethanol intake on isoniazid pharmacokinetics. Eur J Clin Pharmacol. 2004;60(9):679–82.

    CAS  PubMed  Google Scholar 

  165. McDowell JA, Chittick GE, Ravitch JR, et al. Pharmacokinetics of [(14)C] abacavir, a human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, administered in a single oral dose to HIV-1-infected adults: a mass balance study. Antimicrob Agents Chemother. 1999;43(12):2855–61.

    CAS  PubMed Central  PubMed  Google Scholar 

  166. McDowell JA, Chittick GE, Stevens CP, et al. Pharmacokinetic interaction of abacavir (1592U89) and ethanol in human immunodeficiency virus-infected adults. Antimicrob Agents Chemother. 2000;44(6):1686–90.

    CAS  PubMed Central  PubMed  Google Scholar 

  167. Ward BA, Gorski JC, Jones DR, et al. The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther. 2003;306(1):287–300.

    CAS  PubMed  Google Scholar 

  168. McCance-Katz EF, Gruber VA, Beatty G, et al. Interactions between alcohol and the antiretroviral medications ritonavir or efavirenz. J Addict Med. 2013;7(4):264–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  169. Hyland R, Dickins M, Collins C, et al. Maraviroc: in vitro assessment of drug-drug interaction potential. Br J Clin Pharmacol. 2008;66(4):498–507.

    CAS  PubMed Central  PubMed  Google Scholar 

  170. Gruber VA, Rainey PM, Lum PJ, et al. Interactions between alcohol and the HIV entry inhibitor Maraviroc. J Int Assoc Provid AIDS Care. 2013;12(6):375–7.

    PubMed Central  PubMed  Google Scholar 

  171. Koudriakova T, Iatsimirskaia E, Utkin I, et al. Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism-based inactivation of cytochrome P4503A by ritonavir. Drug Metab Dispos. 1998;26(6):552–61.

    CAS  PubMed  Google Scholar 

  172. Benowitz NL, Jones RT. Effects of delta-9-tetrahydrocannabinol on drug distribution and metabolism. Antipyrine, pentobarbital, and ethanol. Clin Pharmacol Ther. 1977;22(3):259–68.

    CAS  PubMed  Google Scholar 

  173. Belgrave BE, Bird KD, Chesher GB, et al. The effect of cannabidiol, alone and in combination with ethanol, on human performance. Psychopharmacology (Berl). 1979;64(2):243–6.

    CAS  PubMed  Google Scholar 

  174. Consroe P, Carlini EA, Zwicker AP, et al. Interaction of cannabidiol and alcohol in humans. Psychopharmacology (Berl). 1979;66(1):45–50.

    CAS  PubMed  Google Scholar 

  175. Perez-Reyes M, Hicks RE, Bumberry J, et al. Interaction between marihuana and ethanol: effects on psychomotor performance. Alcohol Clin Exp Res. 1988;12(2):268–76.

    CAS  PubMed  Google Scholar 

  176. Lukas SE, Benedikt R, Mendelson JH, et al. Marihuana attenuates the rise in plasma ethanol levels in human subjects. Neuropsychopharmacol. 1992;7(1):77–81.

    CAS  Google Scholar 

  177. Lukas SE, Orozco S. Ethanol increases plasma Delta(9)-tetrahydrocannabinol (THC) levels and subjective effects after marihuana smoking in human volunteers. Drug Alcohol Depend. 2001;64(2):143–9.

    CAS  PubMed  Google Scholar 

  178. Ramaekers JG, Theunissen EL, de Brouwer M, et al. Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users. Psychopharmacology (Berl). 2011;214(2):391–401.

    CAS  PubMed Central  PubMed  Google Scholar 

  179. Toennes SW, Schneider K, Kauert GF, et al. Influence of ethanol on cannabinoid pharmacokinetic parameters in chronic users. Anal Bioanal Chem. 2011;400(1):145–52.

    CAS  PubMed  Google Scholar 

  180. Toennes SW, Schneider K, Wunder C, et al. Influence of ethanol on the pharmacokinetic properties of Delta9-tetrahydrocannabinol in oral fluid. J Anal Toxicol. 2013;37(3):152–8.

    CAS  PubMed  Google Scholar 

  181. Langel K, Gjerde H, Favretto D, et al. Comparison of drug concentrations between whole blood and oral fluid. Drug Test Anal. 2014;6(5):461–71.

    CAS  PubMed  Google Scholar 

  182. Sewell RA, Poling J, Sofuoglu M. The effect of cannabis compared with alcohol on driving. Am J Addict. 2009;18(3):185–93.

    PubMed Central  PubMed  Google Scholar 

  183. Berghaus G, Guo B. Medicines and driver fitness-findings from a meta-analysis of experimental studies as basic information to pateints, physicians and experts. In: Kloeden C, McLean A, editors. T95: proceedings of the 13th international conference on alcohol, drugs and traffic safety. August 13-August 18, 1995. Adelaide, Australia. Adelaide: NHMRC, Road Accident Unit, University of Adelaide;1995. p. 295–300.

  184. Ballard ME, de Wit H. Combined effects of acute, very-low-dose ethanol and delta(9)-tetrahydrocannabinol in healthy human volunteers. Pharmacol Biochem Behav. 2011;97(4):627–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  185. Ronen A, Chassidim HS, Gershon P, et al. The effect of alcohol, THC and their combination on perceived effects, willingness to drive and performance of driving and non-driving tasks. Accid Anal Prev. 2010;42(6):1855–65.

    PubMed  Google Scholar 

  186. Chesher GB, Franks HM, Hensley VR, et al. The interaction of ethanol and delta9-tetrahydrocannabinol in man: effects on perceptual, cognitive and motor functions. Med J Aust. 1976;2(5):159–63.

    CAS  PubMed  Google Scholar 

  187. Peck R, Biasotti A, Borland P, et al. The effects of marijuana and alcohol on actual driving performance. Alcohol Drugs Driv. 1989;2:134–54.

    Google Scholar 

  188. Robbe H. Marijuana’s impairing effects on driving are moderate when taken alone but severe when combined with alcohol. Hum Psychopharmacol Clin Exp. 1998;13(Suppl 2):S70–8.

    Google Scholar 

  189. Brzezinski MR, Abraham TL, Stone CL, et al. Purification and characterization of a human liver cocaine carboxylesterase that catalyzes the production of benzoylecgonine and the formation of cocaethylene from alcohol and cocaine. Biochem Pharmacol. 1994;48(9):1747–55.

    CAS  PubMed  Google Scholar 

  190. Farre M, de la Torre R, Gonzalez ML, et al. Cocaine and alcohol interactions in humans: neuroendocrine effects and cocaethylene metabolism. J Pharmacol Exp Ther. 1997;283(1):164–76.

    CAS  PubMed  Google Scholar 

  191. Mendelson J, Jones RT, Upton R, et al. Methamphetamine and ethanol interactions in humans. Clin Pharmacol Ther. 1995;57(5):559–68.

    CAS  PubMed  Google Scholar 

  192. Hernandez-Lopez C, Farre M, Roset PN, et al. 3,4-Methylenedioxymethamphetamine (ecstasy) and alcohol interactions in humans: psychomotor performance, subjective effects, and pharmacokinetics. J Pharmacol Exp Ther. 2002;300(1):236–44.

    CAS  PubMed  Google Scholar 

  193. Ku HY, Ahn HJ, Seo KA, et al. The contributions of cytochromes P450 3A4 and 3A5 to the metabolism of the phosphodiesterase type 5 inhibitors sildenafil, udenafil, and vardenafil. Drug Metab Dispos. 2008;36(6):986–90.

    CAS  PubMed  Google Scholar 

  194. Wensing G, Bauer R, Unger S, et al. Simultaneous administration of vardenafil and alcohol does not result in a pharmacodynamic or pharmacokinetic interaction in healthy male subjects. Int J Clin Pharmacol Ther. 2006;44(5):216–24.

    CAS  PubMed  Google Scholar 

  195. Jacobsen D, Sebastian CS, Dies DF, et al. Kinetic interactions between 4-methylpyrazole and ethanol in healthy humans. Alcohol Clin Exp Res. 1996;20(5):804–9.

    CAS  PubMed  Google Scholar 

  196. Madan A, Parkinson A, Faiman MD. Identification of the human and rat P450 enzymes responsible for the sulfoxidation of S-methyl N, N-diethylthiolcarbamate (DETC-ME). The terminal step in the bioactivation of disulfiram. Drug Metab Dispos. 1995;23(10):1153–62.

    CAS  PubMed  Google Scholar 

  197. Johansson B, Angelo HR, Christensen JK, Møller IW, Rønsted P. Dose-effect relationship of disulfiram in human volunteers. II: a study of the relation between the disulfiram-alcohol reaction and plasma concentrations of acetaldehyde, diethyldithiocarbamic acid methyl ester, and erythrocyte aldehyde dehydrogenase activity. Pharmacol Toxicol. 1991;68(3):166–70.

    CAS  PubMed  Google Scholar 

  198. Wicht F, Fisch HU, Nelles J, et al. Divergence of ethanol and acetaldehyde kinetics and of the disulfiram-alcohol reaction between subjects with and without alcoholic liver disease. Alcohol Clin Exp Res. 1995;19(2):356–61.

    CAS  PubMed  Google Scholar 

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No sources of funding were used to assist in the preparation of this review. L.-N. Chan and G. D. Anderson have no conflicts of interest to declare.

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Chan, LN., Anderson, G.D. Pharmacokinetic and Pharmacodynamic Drug Interactions with Ethanol (Alcohol). Clin Pharmacokinet 53, 1115–1136 (2014). https://doi.org/10.1007/s40262-014-0190-x

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