The role of cytochrome P450 2D6 in the metabolism of moclobemide.
The metabolic fate of moclobemide (Ro 11-1163), a new reversible and selective inhibitor of monoamine oxidase type A (MAO-A), has been assessed in a pilot study in 2 debrisoquine poor metabolizers (PM) and 4 extensive metabolizers (EM) after multiple oral dosings of moclobemide with and without co-medication of dextromethorphan. Absorption and disposition parameters were not different between PM and EM. Concurrent application of dextromethorphan, a selective substrate of CYP2D6, did not affect the pharmacokinetics of moclobemide. These results indicate that the cytochromal isoenzyme CYP2D6 does not play a major role in the metabolic degradation of moclobemide. Limited CYP2D6 activities because of a genetic defect or co-medications with CYP2D6 substrates should therefore not give rise to elevated moclobemide blood levels.
Härtter
S
S
Department of Psychiatry, University of Mainz, Germany.
Dingemanse
J
J
Baier
D
D
Ziegler
G
G
Hiemke
C
C
D000042:Absorption; D000328:Adult; D001549:Benzamides / Q000378:metabolism* / Q000493:pharmacokinetics; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D003577:Cytochrome P-450 Enzyme System; D019389:Cytochrome P-450 CYP2D6; D020912:Moclobemide