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In vitro metabolism of mirtazapine enantiomers by human cytochrome P450 enzymes

✍ Scribed by Seetal Dodd; David W. Boulton; Graham D. Burrows; C. Lindsay De Vane; Trevor R. Norman

Publisher: John Wiley and Sons
Year: 2001
Tongue: English
Weight: 52 KB
Volume: 16
Category: Article
ISSN: 0885-6222
DOI: 10.1002/hup.328

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✦ Synopsis

The metabolism of mirtazapine enantiomers was investigated in vitro using human lymphoblast microsomes transfected with human cDNA to overexpress either CYP1A2, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 and assayed for mirtazapine enantiomers using a validated chiral method of high-performance liquid chromatography. (+)-Mirtazapine was extensively metabolised by CYP2D6 (K(m) = 9.3 +/- 3.3 &mgrmol/l, V(max) = 40.9 +/- 7.9 &mgrmol/h/mg, intrinsic clearance = 4.41 l/h/mg). CYP1A2 and CYP3A4 showed low metabolic activity towards (+)-mirtazapine and (-)-mirtazapine respectively. Neither CYP2C9 nor CYP2C19 appeared to be involved in the metabolism of the enantiomers of mirtazapine. Copyright 2001 John Wiley & Sons, Ltd.

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