CLint values in human and monkey intestinal microsomes and Fg, human(observed) values calculated from pharmacokinetic parameters in humans

CLint values were determined from metabolic stabilities of 18 CYP3A substrates with pooled MIM and HIM. Linearity of metabolic activity for the microsome concentration (0.001–0.2 mg of protein/ml), the substrate concentration (10–200 nM), and the incubation time (15 or 30 min) was confirmed and CLint values were determined. Each value represents the mean of duplicate measurements.

CompoundsCLintFg, human(observed)References
ml/(min · mg protein)
Buspirone0.1300.2270.11aGertz et al., 2008
Carbamazepinec1.00bGérardin et al., 1990
Cisapride0.0880.2040.55aGertz et al., 2008
Cyclosporine0.0630.1720.77aGertz et al., 2008
Diazepam1.00bFriedman et al., 1992; Greenblatt et al., 1980
Diltiazem0.0240.0940.91aSigusch et al., 1994
Felodipine0.8711.4620.53aGertz et al., 2008
Lovastatin2.1433.0190.065aYang et al., 2007
Midazolam0.2040.3580.56aGertz et al., 2008
Nicardipine2.0355.8930.64aUno et al., 2000
Nifedipine0.0570.1560.62aGertz et al., 2008
Nimodipine0.5191.2230.64aFuhr et al., 1998
Nitrendipine0.2210.6420.44aSoons et al., 1991
Quinidine0.1350.92aGertz et al., 2008
Saquinavir1.7995.1330.54aGertz et al., 2008
Simvastatin1.8594.2470.14aGertz et al., 2008
Triazolam0.64aGertz et al., 2008
Verapamil0.2050.7540.71aGertz et al., 2008
  • a Fg, human is the intestinal availability estimated from GFJ interaction studies (eq. 11).

  • b It is reported that the bioavailability of carbamazepine and diazepam is 1.

  • c —, when the remaining amount after incubation for 30 min with 0.2 mg of microsomal protein/ml was >90%, CLint values were not calculated [CLint <0.018 ml/(min · mg protein)].