Anomalous results of studies on drug interaction in man. II. Halofenate (mk-185) and antipyrine, bishydroxycoumarin, and warfarin.
Three highly reproducible experiments on drug interaction in normal human volunteers provided anomalous results: chronic halofenate administration shortened plasma antipyrine and bishydroxycoumarin half-lives but prolonged plasma warfarin half-lives. This dissociation in the effect produced by a chronically administered drug on the metabolism of test drugs has not previously been reported in man. Chronic halofenate administration to rats, mice and dogs stimulated several hepatic microsomal drug-metabolizing systems, including those responsible for bishydroxycoumarin warfarin hydroxylation.
D000328:Adult; D000446:Aldehyde-Lyases / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000097:blood*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003864:Depression, Chemical; D001728:Dicumarol / Q000008:administration & dosage / Q000097:blood*; D004285:Dogs; D004347:Drug Interactions; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D006016:Glycolates / Q000494:pharmacology*; D006207:Half-Life; D006218:Halofenate / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D013268:Stimulation, Chemical; D013997:Time Factors; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood*
D006016:Glycolates; D014859:Warfarin; D001728:Dicumarol; D003577:Cytochrome P-450 Enzyme System; D005037:Ethylmorphine-N-Demethylase; D000446:Aldehyde-Lyases; D006218:Halofenate; D000983:Antipyrine