TABLE 4

In vitro and in vivo parameters for GSK drugs used in the retrospective analysis of DDI predictions

DrugDoseClinical Probe SubstrateAUC RatioCmax BloodFubLiver/BloodP540 InhibitedKiKIkinact
mgμMμMμMmin1
GSK-1400Desipramine0.92.20.003627CYP2D69.0NANA
GSK-1400Midazolam0.92.20.003627CYP3A46.0NANA
GSK-1400Caffeine1.02.20.003627CYP1A26.5NANA
GSK-1400Flurbiprofen1.12.20.003627CYP2C91.5NANA
GSK-2150Atorvastatin1.11.10.00565.9CYP3A41.7NANA
GSK-340Atorvastatin1.00.0190.0008317CYP3A47.0NANA
GSK-380Warfarin1.00.0380.0008317CYP2C921NANA
GSK-450Midazolam0.90.530.2610CYP3A47.5NANA
GSK-450Warfarin1.20.530.2610CYP2C929160.014
GSK-58Nifedipine0.90.970.003517CYP3A450NANA
GSK-67.5Atorvastatin1.00.0540.1813CYP3A412NANA
GSK-75Simvastatin1.50.200.00614.4CYP3A40.184.20.16
GSK-715Simvastatin4.00.780.00614.4CYP3A40.184.20.16
GSK-730Simvastatin6.11.20.00614.4CYP3A40.184.20.16
GSK-880Desipramine2.03.00.3811CYP2D619NANA
GSK-915Midazolam3.20.0370.005344CYP3A40.230.580.072
GSK-915Atorvastatin1.60.0370.005344CYP3A40.140.580.072
GSK-915Nifedipine1.90.0370.005344CYP3A40.500.580.072
GSK-10a50Midazolam1.40.280.00656.9CYP3A44.933.10.020
GSK-10a100Midazolam1.50.470.00656.9CYP3A44.933.10.020
GSK-10a10Midazolam1.50.0680.00656.9CYP3A44.933.10.020
GSK-10a30Midazolam1.80.220.00656.9CYP3A44.933.10.020
GSK-10a120Midazolam3.11.50.00656.9CYP3A44.933.10.020
GSK-10a30Nifedipine1.60.220.00656.9CYP3A44.863.10.020
GSK-10a120Nifedipine1.61.50.00656.9CYP3A44.863.10.020
GSK-1140Atorvastatin0.90.0490.005031CYP3A44.5NANA
GSK-12200Midazolam1.1160.00346.7CYP3A48.5NANA
GSK-12200Flurbiprofen1.0160.00346.7CYP2C95.0NANA
GSK-1375Midazolam1.0120.0000675.5CYP3A450NANA
GSK-1375Flurbiprofen0.9120.0000675.5CYP2C910NANA
GSK-14900Warfarin1.04000.00101.4CYP2C99.0NANA
GSK-14900Cerivastatin2.34000.00101.4CYP2C81.0NANA
GSK-14900Triazolam1.04000.00101.4CYP3A450NANA
GSK-14900Theophylline1.14000.00101.4CYP1A250NANA
GSK-1510Atorvastatin1.10.460.002919CYP3A44.3NANA
GSK-16100Atorvastatin1.00.980.007177CYP3A421NANA
GSK-17400Warfarin1.10.520.093120CYP2C948NANA
GSK-1845Midazolam1.01.60.335.5CYP3A439NANA
GSK-19200Midazolam1.01.40.131.1CYP3A450NANA
GSK-20a300Desipramine5.20.670.169.4CYP2D621NANA
GSK-21800Midazolam1.4910.0102.2CYP3A45.5NANA
GSK-221000Midazolam11140.4219CYP3A431460.074
GSK-23300Midazolam1.71.40.001750CYP3A40.15NANA
GSK-2470Simvastatin1.01.00.0125.0CYP3A41.5NANA
GSK-255Dextromethorphan350.160.454.9CYP2D60.90.90.057
GSK-26200Midazolam2.20.160.05325CYP3A47.56.50.047
  • Fub, fraction unbound in blood; NA, not applicable.

  • a Structures for GSK-10 (casopitant) and GSK-20 (bupropion) are given in Fig. 1.