TABLE 4

Estimated systems and drug parameters in rats and their precision (RSE%)

All IC50/EC50 refer to unbound conc.

Drug vs. SystemParametersEstimates (RSE%)IIV (RSE%)t1/2,kout
min
System parametersBSLHR (beats min−1)317. (1.4)24. (12)
BSLMAP (mm Hg)102. (1.7)7.2 (13)
BSLQT (ms)64.3 (2.1)3.9 (11)
FB00.00532 (0.7)
PHR3.25 (1.1)
PTPR1.21 (2.0)
kout,QT (h−1)9.45 (15)4.4
kout,HR (h−1)30.7 (7.8)1.4
kout,TPR (h−1)3.8 (13)11
kout,SV (h−1)0.115 (1.7)360
IvabradineImax,HR0.944 (1.7)
IC50,HR (nM)475. (11)
γHR0.511 (3.6)
SildenafilImax,TPR1.00 (1.3)
IC50,TPR (nM)4.01 (5.4)
γTPR0.63 (2.5)
DofetilideEmax,QT0.195 (9.9)
EC50,QT (nM)50.6 (93)
γQT0.156 (21)
PimobendanSLSV (nM−1)5.01*10−5 (25)
Imax,TPR0.745 (4.6)
IC50,TPR (nM)47.8 (16)
γTPR0.546 (4.7)
kmet (h−1)0.116 (14)
  • IIV, interindividual variability, S.D. of the parameter within the population; t1/2,kout, equivalent half-lives for kout,.