Comparison of in vitro methods and the in vivo metabolism of lindane for assessing the effects of repeated administration of ethanol on hepatic drug metabolism.
In vitro methods of assessing alterations in drug metabolism and the measurement of lindane metabolites in urine were compared for their ability to determine the influence of ethanol on drug metabolism. Ethanol was administered intraperitoneally (i.p.) to young adult female rats daily for 7 days at doses of 0.12, 0.60 and 3.0 ml/kg. No alterations were observed in ethylmorphine demethylation, hexobarbital oxidation or glucuronyltransferase. Aniline hydroxylation was decreased at the high dose level and aldrin epoxidation was increased at the intermediate dose. In vivo only the high dose of ethanol produced significant changes with significant increases observed for the oxidation of lindane to alcohol metabolites, the glucuronidation of the alcohol but not the chlorophenol metabolites, and glutathione conjugation. The latter increase was also observed in vitro. The in vivo and in vitro data suggest a minimal effect of ethanol on drug metabolism at low levels of administration.
B A
BA
Trela
G P
GP
Carlson
R W
RW
Chadwick
M F
MF
Copeland
D000818:Animals; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D005965:Glucuronates; D004364:Pharmaceutical Preparations; D000431:Ethanol; D001556:Hexachlorocyclohexane; D005978:Glutathione