d-Propoxyphene is a potent inhibitor of debrisoquine, but not S-mephenytoin 4-hydroxylation in vivo.

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Sanz EJ, Bertilsson L

d-Propoxyphene is a potent inhibitor of debrisoquine, but not S-mephenytoin 4-hydroxylation in vivo.

Ther Drug Monit. 1990 May;12(3):297-9. doi: 10.1097/00007691-199005000-00016.

PubMed ID

2349617 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Dextropropoxyphene	Cytochrome P450 2D6	Protein	Humans	Unknown	Substrate Inhibitor	Details