d-Propoxyphene is a potent inhibitor of debrisoquine, but not S-mephenytoin 4-hydroxylation in vivo.
The debrisoquine and S-mephenytoin 4-hydroxylation phenotyping tests were performed in 14 healthy subjects. All were extensive metabolizers of both drugs. After at least 4 weeks, they received a 150 mg tablet of d-propoxyphene and 5 h later the debrisoquine-mephenytoin test was repeated. This single dose of d-propoxyphene caused no change in mephenytoin S/R ratio, but increased the debrisoquine metabolic ratio (MR) in each subject (p less than 0.025). The four subjects with a relatively high MR (5.1-8.3) in the first test had an MR of debrisoquine in the second test ranging between 22 and 40, falsely classifying them as "poor metabolizers" of debrisoquine. This shows that d-propoxyphene is a potent inhibitor of debrisoquine, but not of S-mephenytoin 4-hydroxylase in vivo. A previous in vitro study has shown that d-propoxyphene inhibits the hydroxylation of desipramine, which is a substrate of the debrisoquine hydroxylase.
Sanz
E J
EJ
Department of Clinical Pharmacology, Karolinska Institute, Huddinge Hospital, Sweden.
Bertilsson
L
L
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D003647:Debrisoquin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011431:Dextropropoxyphene / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006827:Hydantoins / Q000037:antagonists & inhibitors*; D006900:Hydroxylation; D007536:Isomerism; D007546:Isoquinolines / Q000037:antagonists & inhibitors*; D008297:Male; D008617:Mephenytoin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011110:Polymorphism, Genetic
D006827:Hydantoins; D007546:Isoquinolines; D008617:Mephenytoin; D011431:Dextropropoxyphene; D003647:Debrisoquin