Chronic treatment with ethanol or chlordiazepoxide alters the metabolism of chlordiazepoxide.
Although chronic ethanol administration in C57BL/6J mice did not cause an induction of ethanol metabolism, it altered the metabolism of chlordiazepoxide (CDP). Significantly lower blood levels of CDP, but higher levels of N-desmethyl CDP (NDCDP), were observed in ethanol-dependent mice compared to pair-fed controls during the first hour after CDP injection. Mice treated chronically with CDP showed significantly lower blood levels of CDP and NDCDP than pair-fed controls after a test dose of CDP. In response to an injection of ethanol, the CDP-dependent mice had lower blood alcohol levels (BAL) than the pair-fed controls, but the rate of fall of BAL was not different in the two groups. Thus, chronic CDP treatment affected the absorption and distribution of ethanol. These results provide a metabolic basis for the manifestations of CDP tolerance and ethanol cross-tolerance that have been reported in CDP-dependent mice.
Chan
A W
AW
Research Institute on Alcoholism, New York State Division of Alcoholism and Alcohol Abuse, Buffalo 14203.
Schanley
D L
DL
Langan
M C
MC
Leong
F W
FW
Penetrante
M L
ML
D000818:Animals; D002707:Chlordiazepoxide / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D004032:Diet; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D000431:Ethanol; D002707:Chlordiazepoxide; C015784:N-demethylchlordiazepoxide