Extemporaneous Compounding and Physiological Modeling of Amlodipine/Valsartan Suspension

Table 2

Simulation input data.

Parameter	Value
	Amlodipine (as besylate)	Valsartan
Molecular weight (g/mole)	567.051	435.53
Partition/distribution coefficient	2.66 (pH = 7.4)^a	−0.34 (pH = 7)^b
Pka1	8.7^c	3.9^d
Pka2	—	4.73^d
Solubility (mg/ml)	0.774 (pH 7.4)^e	16.8 (pH = 8)^f
Peff (human jejunal permeability) (cm/sec)	0.0743 ∗ 10^−4g (caco-2)	0.262 ∗ 10^−4h (rat)
Dose (mg)	5	80
Dose volume (ml)	250	250
Mean precipitation time (sec)	900^i	900^i
Diffusion coefficient (cm^2/s)	4.2 ∗ 10^−8j	1.1 ∗ 10^−8k
Drug particle density (g/ml)	1.2^i	1.2^i
Blood plasma concentration ratio	1^i	1^i
Body weight (kg)	70	70
Unbound percent in plasma (%)	2^l	5^m
Clearance (l/hr)	28^n	f^n
Volume of distribution, Vc (L/Kg)	17^n	0.23^n
Elimination half-life (h)	27.03^o	5.58^o
Simulation time (hr)	144	72

^aFrom [17, 18], ^bfrom [19], ^cfrom [20, 21], ^d,ffrom[22], ^efrom [23], ^g from[18], ^hfrom [24], ⁱfrom GastroPlus default values, ^{j, k}from[25], ^lfrom [26], ^mfrom [27], ⁿGastroPlus calculated using PBPKPlus™ module, and ^oGastroPlus calculated (built-in calculation from PK parameters).