TABLE 3

IC50 values for inhibition of different CYP3A microsomal preparations

Experiments were conducted in triplicate with 4 μM midazolam using midazolam 1′-hydroxylation as a marker of CYP3A activity. Values reported are mean ± S.D. for human liver microsomal incubations, and mean ± S.E. of the model fit for CYP3A Supersomes. No statistical tests were performed for comparison of Supersomes.


Inhibitor

HL Microsomes

Supersomes
CYP3A4 (n = 18)
CYP3A5 (n = 14)
CYP3A4 + b5
CYP3A5 + b5
Ketoconazole (nM) 22.4 ± 6.6 53.7 ± 29* 24.9 ± 3.8 145 ± 24
Erythromycin (μM) 15.4 ± 8.0 21.7 ± 7.5* 39.4 ± 1.0 64.2 ± 6.0
Diltiazem (μM) 128 ± 63 105 ± 21 62.3 ± 12 117 ± 96
Nicardipine (nM)
349 ± 86
519 ± 147*
24.5 ± 4.3
33.0 ± 6.3
  • * Significant difference between CYP3A5 and CYP3A4, p < 0.05.