FORMATION OF MEPROBAMATE FROM CARISOPRODOL IS CATALYZED BY CYP2C19

Carisoprodol is a muscle relaxant analgesic, which has an active metab olite i.e. meprobamate, We conducted an open three-panel single-dose a dministration study with 15 healthy volunteers: five poor metabolizers of mephenytoin, five poor metabolizers of debrisoquine and five exten sive metabolizers of both substrates, The aim was to investigate if th e elimination of carisoprodol and meprobamate is dependent on the two metabolic polymorphisms of mephenytoin and debrisoquine. The subjects were given single oral doses of 700 mg carisoprodol and 400 mg meproba mate on separate occasions. The disposition of carisoprodol was clearl y correlated to the mephenytoin hydroxylation phenotype, The mean seru m clearance of carisoprodol was four times lower in poor metabolizers of mephenytoin than in extensive metabolizers, which confirms the hypo thesis from our previous study that N-dealkylation of carisoprodol cos egregates with the mephenytoin hydroxylation polymorphism, However, me an serum clearance of meprobamate did not differ between the two group s, Also, polymorphic debrisoquine hydroxylation did not influence the elimination of carisoprodol or meprobamate, Poor metabolizers of mephe nytoin thus have a lower capacity to metabolize carisoprodol and may t herefore have an increased risk of developing concentration dependent side-effects such as drowsiness and hypotension, if treated with ordin ary doses of carisoprodol.