TABLE 2

Kinetic parameters (mean ± S.D.) for the formation of 8-hydroxyefavirenz from efavirenz in 15 human liver microsomal samples with CYP2B6*1/*1, CYP2B6*1/*6, and CYP2B6*6/*6 genotypes (n = 5 HLMs for each genotype)

Efavirenz (1–200 μM) was incubated with human liver microsomal samples (0.25 mg/ml) with CYP2B6*1/*1, CYP2B6*1/*6, and CYP2B6*6/*6 genotypes (n = 5 HLM for each genotype) and a NADPH-generating system at 37°C for 15 min in duplicate. Kinetic parameters (V_max and K_m) for the formation of 8-hydroxyefavirenz were estimated by fitting the velocity versus efavirenz concentrations to the simple single-site Michaelis-Menten equation. In vitro Cl_int was calculated as V_max/K_m. The kinetic parameters (V_max, K_m, and Cl_int) for each genotype group are listed in Supplemental Table 1. The data presented here are mean ± S.D. calculated from five individual HLM values for each genotype.