TABLE 1

Effect of efavirenz on the midazolam 1′-hydroxylation by HLM, rCYP3A4, and rCYP3A5

All experiments were performed in triplicate. The kinetic parameters were calculated by nonlinear regression analysis (Michaelis-Menten, eq. 1). Data are presented as means ± S.D.

Efavirenz, μMVmaxaKmVmax/Kmb
μM
Human liver microsomes
    00.38 ± 0.032.4 ± 0.7158.3
    0.50.44 ± 0.052.2 ± 0.9200.0
    10.49 ± 0.052.1 ± 0.5233.3
    50.58 ± 0.051.2 ± 0.3483.3
rCYP3A4
    01.3 ± 0.20.8 ± 0.21.6
    51.8 ± 0.21.6 ± 0.51.1
rCYP3A5
    03.9 ± 0.31.2 ± 0.33.3
    55.0 ± 0.51.3 ± 0.53.8

  • ↵a Units are nmol · min−1 · mg protein−1 for HLM and pmol · min−1 · pmol P450−1 for rCYP3A4 and rCYP3A5.

  • ↵b For intrinsic clearance (Vmax/Km ratio), units are μl · min−1 · mg protein−1 for HLM and μl · min−1 · pmol P450−1 for rCYP3A4 and rCYP3A5.