TABLE 4

Comparison of Simcyp-simulated inhibitor concentrations with clinical observations

InhibitorSubstrateObserved Inhibitor Conc.Simulated Inhibitor Conc.References for Observed Inhibitor Conc.
Mean CmaxMean AUC0–8 hMean CmaxMean AUC0–8 h
ng/mlmg/l · hng/mlmg/l · h
Clarithromycin, 500 mgMidazolam150010.7a180010.3aWang et al., 2004a
Clarithromycin, 500 mgZolpidem260016.3234711.4Farkas et al., 2009
Diltiazem IR, 60 mgMidazolam700.4780.50.42Backman et al., 1994
Diltiazem IR, 60 mgTriazolam105.90.6290.10.44Varhe et al., 1996
Diltiazem SR, 120 mgSimvastatin132.8b1.47a114.31.26aMousa et al., 2000
Diltiazem SR, 240 mg—c1662.37d1592.41dRobbins-Weilert et al., 1999
Erythromycin, 500 mgMidazolam p.o.300019.6d,e144923.8dOlkkola et al., 1993
Erythromycin, 500 mgMidazolam i.v.120019.6b,d141023.1dOlkkola et al., 1993
Erythromycin, 500 mgSimvastatinN.A.26.1d122825.1dKantola et al., 1998
Ritonavir, 300–500 mgSildenafil15,792127.1916798.6Muirhead et al., 2000
Ritonavir, 200 mgAlprazolam270016.8281122.1Greenblatt et al., 2000a
Ritonavir, 200 mgTriazolam175012.1323929.0Greenblatt et al., 2000b
Ritonavir, 200 mgZolpidem270014.7338530.7Greenblatt et al., 2000b
Saquinavir, 1200 mgSildenafil18596.01334.91.84Muirhead et al., 2000
Saquinavir, 1200 mgMidazolam2973.45321.51.67Palkama et al., 1999
Verapamil IR, 80 mgMidazolam850.37699.90.60Backman et al., 1994
Verapamil IR, 80 mgSimvastatinN.A.0.97d95.71.80dKantola et al., 1998
Verapamil SR, 240 mg—c2171.93d164.31.94dDilger et al., 1999
Fluoxetine, 20 mgZolpidem133.52.67d45.90.94dAllard et al., 1998
Fluoxetine, 20 mgZolpidem85.41.68d42.60.85dPiergies et al., 1996

  • N.A., not available.

  • ↵a AUC0–12 h.

  • ↵b Lefebvre et al., 1994.

  • ↵c —, no affected substrate,

  • ↵d AUC0–24 h.

  • ↵e Brannan et al., 1995.