In vitro metabolism of mirtazapine enantiomers by human cytochrome P450 enzymes

The metabolism of mirtazapine enantiomers was investigated in vitro using h uman lymphoblast microsomes transfected with human cDNA to overexpress eith er CYP1A2, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 and assayed for mirtazapine en antiomers using a validated chiral method of high-performance liquid chroma tography. (+)-Mirtazapine was extensively metabolised by CYP2D6 (K-m = 9.3 +/- 3.3 mu mol/l, V-max = 40.9 +/- 7.9 mu mol/h/mg, intrinsic clearance = 4 .41 l/h/mg). CYP1A2 and CYP3A4 showed low metabolic activity towards (+)-mi rtazapine and (-)-mirtazapine respectively. Neither CYP2C9 nor CYP2C19 appe ared to be involved in the metabolism of the enantiomers of mirtazapine. Co pyright (C) 2001 John Wiley & Sons, Ltd.