Ethanol interaction with propoxyphene and norpropoxyphene metabolism in isolated rat hepatocytes.
Suspensions of isolated rat hepatocytes (approximately 7.5 X 10(5) cells/ml) metabolized added propoxyphene and norpropoxyphene rapidly. At 2 microM, the metabolism of both drugs obeyed first-order elimination kinetics. Increasing propoxyphene concentrations (1, 2, 4 and 8 microM) gradually increased the medium concentrations of norpropoxyphene. The total propoxyphene metabolism was the same at 4 and 8 microM. The effect of ethanol (10 and 60 mM) on propoxyphene (2 microM) and norpropoxyphene (2 microM) metabolism in suspensions of isolated rat hepatocytes was studied. The half-lives of propoxyphene were 7.1 +/- 5.5 min in absence and 6.7 +/- 2.8 min in presence of 10 mM ethanol, but increased to 10.7 +/- 5.8 min in presence of 60 mM ethanol (p less than 0.05). The half-lives of added norpropoxyphene increased from 17.9 +/- 4.1 min to 26.0 +/- 7.3 min at 10 mM ethanol (p less than 0.05) and 29.3 +/- 5.9 min at 60 mM ethanol (p less than 0.05). Ethanol (60 mM) reduced the elimination rate constant of propoxyphene and norpropoxyphene by 31 +/- 25% and 38 +/- 15%, respectively.
D000818:Animals; D011431:Dextropropoxyphene / Q000031:analogs & derivatives* / Q000378:metabolism*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000431:Ethanol; C002756:norpropoxyphene; D011431:Dextropropoxyphene