Induction of hepatic enzymes by methaqualone and effect on warfarin-induced hypoprothrombinemia.
The effect of methaqualone on the induction of hepatic enzymes was evaluated in rats and compared with that of phenobarbital by measuring effects on hexobarbital and methaqualone hypnosis, plasma and tissue levels of methaqualone, hepatic aniline hydroxylase and aminopyrine demethylase activity and warfarin-induced hypoprothrombinemia. Maximal reductions in hexobarbital hypnosis occurred 3 days after daily administration of 60 mg of methaqualone per kg per day. At this time, the activities of aniline hydroxylase and aminopyrine demethylase were increased 60 and 139%, respectively, and hepatic microsomal proteins increased 15% above controls in methaqualone-pretreated animals. Methaqualone altered its own metabolism as demonstrated by a 48% reduction in methaqualone hypnosis in pretreated animals. The extent and duration of induction by phenobarbital was considerably greater than methaqualone in all experiments. Methaqualone pretreatment did not affect warfarin-induced hypoprothrombinemia, whereas phenobarbital-pretreated animals showed a 32 to 64% reduction in response to the anticoagulant. These studies indicate that methaqualone is a relatively weak inducer of hepatic drug-metabolizing enzymes and has no effect on the anticoagulant acitivty of warfarin.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects*; D006591:Hexobarbital / Q000494:pharmacology; D007020:Hypoprothrombinemias / Q000139:chemically induced* / Q000503:physiopathology; D008099:Liver / Q000201:enzymology*; D008297:Male; D008702:Methaqualone / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D011517:Prothrombin Time; D051381:Rats; D012890:Sleep / Q000187:drug effects; D013997:Time Factors; D014859:Warfarin / Q000494:pharmacology*
D014859:Warfarin; D008702:Methaqualone; D011335:Proadifen; D006591:Hexobarbital; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D010634:Phenobarbital