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Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: A panel study *
Author(s) -
Gram Lars F.,
Guentert Theodor W.,
Grange Susan,
Vistisen Kirsten,
Brøsen Kim
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90230-9
Subject(s) - mephenytoin , moclobemide , cyp2c19 , pharmacology , cyp2d6 , chemistry , cyp1a2 , medicine , biochemistry , metabolism , cytochrome p450 , antidepressant , hippocampus
The reversible monoamine oxidase A inhibitor moclobemide was given in single (300 mg) and multiple doses (600 mg/day) to 11 male and four female healthy volunteers (age range, 23 to 27) who were either poor metabolizers of S ‐mephenytoin ( n = 7) or extensive metabolizers of S ‐mephenytoin ( n = 8). All were extensive metabolizers of sparteine. Poor metabolizers of S ‐mephenytoin had lower moclobemide clearance values (median, single dose: 16.1 versus 43.2 L · hr −1 ; steady state: 13.4 versus 22.1 L · hr −1 and longer moclobemide half‐life values (median, single dose: 4.0 versus 1.8 hours; steady state: 5.1 versus 2.7 hours) than extensive metabolizers of S ‐mephenytoin. The plasma levels of a metabolite formed by C‐hydroxylation (Ro 12‐8095) were lower in poor metabolizers of S ‐mephenytoin than in extensive metabolizers of S ‐mephenytoin. Moclobemide thus partially undergoes oxidative metabolism by way of the polymorphic CYP2C19. A combined mephenytoin, sparteine, and caffeine test performed before, during, and after multiple dosing of moclobemide showed changes in the metabolic indexes compatible with a reversible inhibition of oxidation by way of the corresponding CYP enzymes—CYP2C19, CYP2D6, and CYP1A2—during moclobemide treatment. Clinical Pharmacology & Therapeutics (1995) 57 , 670–677; doi: