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. 1978 Nov 4;2(6147):1260–1262. doi: 10.1136/bmj.2.6147.1260

Ethanol-induced increase in drug acetylation in man and isolated rat liver cells.

H Olsen, J Mørland
PMCID: PMC1608489  PMID: 709306

Abstract

Sixteen healthy volunteers took part in a cross-over study examining the effect of ethanol on the rate of sulphadimidine acetylation (blood ethanol concentration about 1 g/1). In both rapid and slow acetylators the apparent half life of the drug decreased by about 20% after ethanol (mean reduction 39 +/- SE 8 min) and the amount of drug acetylated, measured in blood and urine, increased. In three slow acetylators the rate of acetylation in blood increased so noticeably after ethanol that they would otherwise have been classified as rapid acetylators. Suspensions of isolated rat liver cells showed an increase of about 30% in the rate of sulphadimidine acetylation after the addition of ethanol (2 g/1). Patients' usual alcohol consumption should be taken into account in determining their acetylator status.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bevill R. F., Sharma R. M., Meachum S. H., Wozniak S. C., Bourne D. W., Dittert L. W. Disposition of sulfonamides in food-producing animals: concentrations of sulfamethazine and its metabolites in plasma, urine, and tissues of lambs following intravenous administration. Am J Vet Res. 1977 Jul;38(7):973–977. [PubMed] [Google Scholar]
  3. Evans D. A. An improved and simplified method of detecting the acetylator phenotype. J Med Genet. 1969 Dec;6(4):405–407. doi: 10.1136/jmg.6.4.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. FORSANDER O. A., RAIHA N. C. Metabolites produced in the liver during alcohol oxidation. J Biol Chem. 1960 Jan;235:34–36. [PubMed] [Google Scholar]
  5. Forsander O. A., Lindros K. O. Influence of ethanol on the acetyl-coenzyme A level of intact rat liver. Acta Chem Scand. 1967;21(9):2568–2568. doi: 10.3891/acta.chem.scand.21-2568. [DOI] [PubMed] [Google Scholar]
  6. Hänninen O., Alanen K. The competitive inhibition of p-nitrophenyl-beta-D-glucopyranosiduronic acid synthesis by aliphatic alcohols in vitro. Biochem Pharmacol. 1966 Oct;15(10):1465–1467. doi: 10.1016/0006-2952(66)90191-2. [DOI] [PubMed] [Google Scholar]
  7. LESTER D. THE ACETYLATION OF ISONIAZID IN ALCOHOLICS. Q J Stud Alcohol. 1964 Sep;25:541–543. [PubMed] [Google Scholar]
  8. Mitchell J. R., Thorgeirsson U. P., Black M., Timbrell J. A., Snodgrass W. R., Potter W. Z., Jollow H. R., Keiser H. R. Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydranize metabolites. Clin Pharmacol Ther. 1975 Jul;18(1):70–79. doi: 10.1002/cpt197518170. [DOI] [PubMed] [Google Scholar]
  9. Moldéus P., Vadi H., Berggren M. Oxidative and conjugative metabolism of p-nitroanisole and p-nitrophenol in isolated rat liver cells. Acta Pharmacol Toxicol (Copenh) 1976 Jul;39(1):17–32. doi: 10.1111/j.1600-0773.1976.tb03151.x. [DOI] [PubMed] [Google Scholar]
  10. Morland J., Olsen H. Metabolism of sulfadimidine, sulfanilamide, p-aminobenzoic acid, and isoniazid in suspensions of parenchymal and nonparenchymal rat liver cells. Drug Metab Dispos. 1977 Nov-Dec;5(6):511–517. [PubMed] [Google Scholar]
  11. NELSON E. Zero order oxidation of tolbutamide in vivo. Nature. 1962 Jan 6;193:76–77. doi: 10.1038/193076b0. [DOI] [PubMed] [Google Scholar]
  12. Rubin E., Gang H., Misra P. S., Lieber C. S. Inhibition of drug metabolism by acute ethanol intoxication. A hepatic microsomal mechanism. Am J Med. 1970 Dec;49(6):801–806. doi: 10.1016/s0002-9343(70)80061-4. [DOI] [PubMed] [Google Scholar]
  13. Rubin E., Lieber C. S. Hepatic microsomal enzymes in man and rat: induction and inhibition by ethanol. Science. 1968 Nov 8;162(3854):690–691. doi: 10.1126/science.162.3854.690. [DOI] [PubMed] [Google Scholar]
  14. Schüppel R. Konjugationsreaktionen im Arzneistoffwechsel der Ratte bei akuter Athanolbelastung. Naunyn Schmiedebergs Arch Pharmakol. 1969;265(3):233–243. [PubMed] [Google Scholar]
  15. Soehring K., Schüppel R. Wechselwirkungen zwischen Alkohol und Arzneimitteln. Dtsch Med Wochenschr. 1966 Oct 21;91(42):1892–1896. doi: 10.1055/s-0028-1111611. [DOI] [PubMed] [Google Scholar]
  16. Thomas B. H., Solomonraj G. Drug interactions with isoniazid metabolism in rats. J Pharm Sci. 1977 Sep;66(9):1322–1326. doi: 10.1002/jps.2600660930. [DOI] [PubMed] [Google Scholar]
  17. WARIS E. Effect of ethyl alcohol on some coagulation factors in man during anticoagulant therapy. Ann Med Exp Biol Fenn. 1963;41:45–53. [PubMed] [Google Scholar]

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