TABLE 2

Summary of drug-related parameters used in the current PBPK model for 12 drugs investigated

References for logP_o:w, pK_a, fu_p, k_a, and K_m are found in Supplemental Table 1 and at http://www.pharmacy.manchester.ac.uk/capkr/.

	Dose	k_a^{^a}	C_ent	logP_o:w	pK_a	fu_p	R_b	P_eff^{^b}	K_m^{^c}	In Vivo CL_{int, h}^{^d}	In Vitro CL_{int, h}^{^e}
	mg	h⁻¹	μM					μm/s	μM	l/h	l/h
Atorvastatin	40	3.7	15	4.07	4.46	0.051	0.61	1.72	33	1990	213
Buspirone	20	5.0	14	2.63	7.32, 4.12	0.05	0.81	7.17	8.0	20,700^{^f}	963
Cyclosporine^{^g}	380	2.0	32	3.45	Neutral	0.019^{^h}	1.36	3.30	1.4	1450	279
	570	1.1	14
Felodipine	10	2.8	4.0	3.86	Neutral	0.0048	0.70	3.00	5.3	39,100	7150
Indinavir^{^g}	400	1.8	57	2.92	5.9, 3.7	0.36	0.84	2.07^ⁱ	0.1	1120	2090
Lovastatin	20	0.8	9.0	4.26	Neutral	0.017	0.57	5.05	7.8	5750^{^f}	17,200
Midazolam	3	4.2	2.2	3.25	6.1	0.031	0.55	6.73	3.3	1610	1540
Nisoldipine	20	3.0	8.6	3.80	Neutral	0.0041	1.0	4.05	2.1	38,900	25,200
Saquinavir^{^g}	600	2.5	37	4.10	8.2	0.028	0.74	3.33^ⁱ	0.3	7660^{^f}	26,800
Simvastatin	40	2.0	10	4.71	Neutral	0.014	0.57	4.30	3.4	14,300^{^f}	25,500
Tacrolimus	0.05 mg/kg	2.6	0.7	3.26	Neutral	0.013^{^h}	35	5.95^ⁱ	2.6	7530	3750
Terfenadine	120	2.8	47	5.62	9.7	0.03	1.0	5.43^ⁱ	1.0	70,600	12,400

logP_o:w, partitioning coefficient between octanol and water; P_app(A-B), apparent permeability (apical-basolateral).
a Estimation of k_a was based on clinical data using
b Estimated from P_app(A-B) data in MDCK-MDR1 cells (Gertz et al., 2010); for cyclosporine, in vivo P_eff data were used (Supplemental Table 1).
c Represent the unbound K_m values (if original studies reported microsomal protein concentration).
d Values reported in Gertz et al. (2010); updated fu_p values for atorvastatin, cyclosporine, felodipine, lovastatin, nisoldipine, simvastatin, and tacrolimus in comparison to Gertz et al. (2010).
e Data represent means from three human liver microsome pools (Gertz et al., 2010).
f In vivo intrinsic clearance was estimated from oral data; for buspirone intravenous clearance exceeded hepatic blood flow and showed very large interindividual variability (Gammans et al., 1986).
g Fraction absorbed of cyclosporine (Neoral and Sandimmune, 0.9 and 0.5, respectively), indinavir, and saquinavir (Invirase) 0.8 and 0.3, respectively.
h Based on equilibrium dialysis experiments in stainless steel chambers.
i Based on P_app(A-B) data in the presence of a P-glycoprotein inhibitor.