. 2021 May 1;110(2):432–442. doi: 10.1002/cpt.2227

Table 2.

Predicted K_{p,uu,brain,pred} using method 2 (5C model)

Compound	Exp.	f_u,m	In vitro Cl_int,i (µl/s/mg prot)	In vitro Cl_int,P‐gp (µl/s/mg prot)	P‐pg abundance in vitro (pmol/mg prot)	IVIV Extrapolated CL_i (mL/min)^a	IVIV Extrapolated CL_P‐gp (mL/min)^a	K_{p,uu,brain,pred(method 2)} ^a	K_{p,uu,brain,obs} (CI_95%)	P/O
Verapamil	1	5.99e‐4	3.08	2.43	1.25	179 ± 33	1,014 ± 590	0.19 ± 0.13	0.16 (0.13–0.20)	1.18
	2	4.50e‐4	3.14	6.17	1.15
	3	2.39e‐4	3.97	3.87	1.16
	4	7.51e‐4	2.56	4.28	2.09
N‐desmethyl loperamide	1	4.59e‐4	3.28	19.5	0.97	287 ± 88	18,503 ± 12,011	0.020 ± 0.014	0.046 (0.035–0.057)	0.44
	2	3.41e‐4	0.44	65.1	1.83
	3	1.41e‐4	6.16	150	9.20
	4	5.00e‐4	6.66	476	11.90
Metoclopramide	1	1	5.19	5.36	9.20	279 ± 58	189 ± 83	0.61 ± 0.10	0.57 (0.46–0.67)	1.08
	2	1	3.74	0.99	7.70
	3	1	6.22	5.65	11.69
	4	1	4.76	6.34	15.67

Predicted K_{p,uu,brain,pred} using method 2, i.e., by extrapolating in vitro intrinsic clearances, obtained from fitting the five‐compartmental model to the in vitro Transwell data, to in vivo using the relative expression factor (for P‐gp–mediated CL) and BMEC protein content (for passive CL).

BMEC, brain microvascular endothelial cells; CI_95%, 95% confidence interval; CL, clearance; Cl_i, in vivo passive unbound into membrane (equal to that out of the membrane); Cl_int,i, passive intrinsic uptake clearance into the membrane; Cl_int,P‐gp, P‐gp–mediated intrinsic clearance; Exp., experiment; f_u,m, unbound fraction in membranes; IVIV, in vitro–to–in vivo; K_p,uu,brain, unbound brain‐to‐plasma concentration ratio; P‐gp, P‐glycoprotein; P/O, predicted/observed value; Prot, protein.

^{^a}

Mean ± standard deviation.