Fig. 3. Influence of P450 isoform-selective chemical inhibitors on methadone N -demethylation by human liver microsomes (HLMs). Results are shown for five livers ( A – E ). CYP3A4 and CYP2B6 contents (respectively, pmol/mg protein) are shown in parentheses . Inhibitors were troleandomycin (TAO, 100 μm), clopidogrel (CGL, 1 μm), and (+)- N -3-benzyl-nirvanol (NBN, 1 μm). R - and S -EDDP formation was determined from 2 μm RS -methadone. Results are the mean ± SD (n = 3). Control rates of R - and S -EDDP formation (pmol · min−1· mg protein−1) were as follows: HLM-139, 21 ± 1 and 35 ± 2; HLM-141, 32 ± 1 and 58 ± 2; HLM-111, 12 ± 1 and 13 ± 1; HLM-120, 12 ± 1.0 and 16 ± 1; HLM-135, 44 ± 3 and 68 ± 3, respectively. * Significantly different from control ( P < 0.05). † Significantly different from troleandomycin ( P < 0.05). EDDP = 2-ethyl-1,5- dimethyl-3,3-diphenylpyrrolidine.