Inhibition of dextromethorphan metabolism by moclobemide.

Abstract:

:This pilot study was conducted to evaluate the potential of the new antidepressant moclobemide to inhibit the cytochrome enzyme P4502D6 (CYP2D6) using the cough suppressant dextromethorphan as a substrate in four extensive metabolizers (EM) of debrisoquine. The subjects received seven oral doses of 20 mg dextromethorphan at 4-h intervals over 2 days (1 and 2) and subsequently moclobemide (300 mg b.i.d.) for 9 days. On days 10 and 11, they received seven doses of 20 mg dextromethorphan in addition to moclobemide. During monotreatment and combined treatment, blood was collected on days 2 and 11, respectively, for determination of dextromethorphan and its demethylated metabolites using automated high-performance liquid chromatography with column switching. Concurrent administration of moclobemide markedly reduced the O-demethylation of dextromethorphan, whereas the N-demethylation of dextrorphan to hydroxymorphinan was not affected. The findings indicate that moclobemide can affect the pharmacokinetics of drugs that are mainly metabolized by CYP2D6.

journal_title

Psychopharmacology

authors

Härtter S,Dingemanse J,Baier D,Ziegler G,Hiemke C

doi

10.1007/s002130050481

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

22-6

issue

1

eissn

0033-3158

issn

1432-2072

journal_volume

135

pub_type

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