TABLE 4

Summary of in vivo pharmacokinetic parameter values in humans and cynomolgus monkeys

Mean values were used for CLh, F, and FaFg. For Li and HT, it was assumed that fe after oral administration was equal to F. MDZ in cynomolgus monkey was taken from Sakuda et. al., 2006.

DrugsSpeciesDose (i.v./p.o.)CLtfeCLhFFaFgFh
mg/kgml/min/kg%ml/min/kg%
LithiumHuman(−/0.25)0.4 ± 0.2No data0a94.5 ± 15.80.951a
Monkey0.14/0.270.7 ± 0.1No data0a97.9 ± 6.80.981a
HydrochlorothiazideHuman(−/0.32)3.0 ± 1.060.20a60.20.601a
Monkey1/15.9 ± 2.0No data0a30.7 ± 9.40.311a
DexamethasoneHuman0.17/0.172.7 ± 0.810.8 ± 4.32.481.4 ± 15.80.930.88
Monkey0.25/0.54.5 ± 0.8No data4.578.9 ± 9.80.850.93
NifedipineHuman0.02/0.278.2 ± 0.6No data8.241.2 ± 5.40.890.46
Monkey0.1/115.6 ± 3.50.05715.69.3 ± 4.00.190.48
MidazolamHuman0.013/0.0264.7 ± 1.50.27 ± 0.074.730.0 ± 10.00.450.67
Monkey1/312.9 ± 1.8<1%12.92.0 ± 0.40.030.62
QuinidineHuman4.3/5.03.8 ± 0.335.1 ± 1.82.579.5 ± 15.00.960.83
Monkey1/312.8 ± 0.70.6 ± 0.212.74.5 ± 1.70.070.62
TacrolimusHuman0.02/0.050.5 ± 0.10.04 ± 0.020.523.3 ± 16.70.240.98
Monkey0.004/0.022.6 ± 0.3No data2.60.5 ± 0.50.0050.94
VerapamilHuman0.14/1.1411.8 ± 0.5No data11.818.0 ± 10.10.470.38
Monkey1/344.9 ± 10.51.5 ± 0.744.20b0.00
DigoxinHuman0.01/0.012.9 ± 0.680.5 ± 3.20.665.3 ± 22.50.670.97
Monkey0.1/0.12.9 ± 0.0317.1 ± 9.32.445.0 ± 14.00.480.94
PropranololHuman0.13/0.511.6cNo data11.6290.780.37
Monkey0.3/124.3 ± 2.4No data24.33.3 ± 1.50.100.34
AmitriptylineHuman0.6/1.212.5 ± 2.3No data12.547.7 ± 11.01d0.30
Monkey0.3/135.8 ± 8.80.2 ± 0.235.71.3 ± 1.00.030.41
TimololHuman0.025/0.47.7 ± 3.7No data7.761.0 ± 19.21d0.56
Monkey0.3/113.6 ± 0.44.8 ± 2.61310.8 ± 4.30.150.71
IbuprofenHuman2.9/4.20.8 ± 0.2No data0.8102.8 ± 12.01d0.93
Monkey1/37.9 ± 0.718.5 ± 1.16.4103.4 ± 14.21d0.76
  • a Assuming CLh was 0, e.g., the Fh values were 1.

  • b Not calculated.

  • c CLt was calculated by dividing dose by AUC after intravenous administration.

  • d The calculated values were greater than 1.