TABLE 7

Comparison of CYP3A inactivation between HLM-predicted potency and the potency observed in cryopreserved human hepatocytes

Amprenavir
Diltiazem
Erythromycin
Raloxifene
Troleandomycin
kinact (min-1) 0.45 0.012 0.072 0.36 0.032
K1 (μM) 0.64 0.48 15.2 18.7 2.39
IC50, Predicteda (μM) 0.02 12.32 2.90 0.62 1.35
IC50, Correctedb (μM) 0.36c 2.41 N.C. 1.01c N.C.
IC50, Nominal (μM)
1.09
3.22
18.02
4.85
2.14

  • N.C., not calculated.

  • ↵ a Obtained from eqs. 2 and 3 using HLM parameters

  • ↵ b Iu that is required to produce 50% inactivation observed in hepatocytes

  • ↵ c [Ī] used for the determination of IC50, Corrected