1. Stereoselective metabolism of S- and R-bupropion to S,S- and R,R-OH-bupropion by recombinant P450 enzymes and human liver microsomes.
Stereoselective metabolism of S- and R-bupropion to S,S- and R,R-OH-bupropion by recombinant P450 enzymes and human liver microsomes. (A and B) Formation of R,R- and S,S-OH-bupropion from 100 µM (A) or 1 µM (B) R- or S-bupropion with a P450 supersome panel. (C) Inhibition of R,R- and S,S-OH-bupropion formation from 1 µM R- or S-bupropion by P450 isoform-specific inhibitors and CYP2B6-specific inhibitory antibody (MAB-2B6). Control 1 is the control for the reversible inhibitors montelukast (2C8 MONT), sulfaphenazole (2C9 SULF), (+)-N-3-benzylnirvanol (2C19 N-BENZ), and quinidine (2D6 QUIN). Control 2 is the control for time-dependent inhibitors troleandomycin (3A4 TAO) and furafylline (1A2 FURA). *p < 0.05 in comparison with control, one-way analysis of variance. (D–F) Formation kinetics of R,R-OH-bupropion from R-bupropion by CYP2C19 (D), CYP3A4 (E), and CYP2B6 (F) supersomes. (G–I) Formation kinetics of S,S-OH-bupropion from S-bupropion by CYP2C19 (G), CYP3A4 (H), and CYP2B6 (I) supersomes. For CYP3A4 incubations with S-bupropion, the two lowest substrate concentrations did not result in sufficient product formation for quantification and these data points are not shown.
Jennifer E. Sager et al. Drug Metab Dispos 2016;44:
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