. Author manuscript; available in PMC: 2017 Feb 5.

Published in final edited form as: Chem Res Toxicol. 2016 Jul 5;29(12):1903–1911. doi: 10.1021/acs.chemrestox.6b00136

Table 2.

Mean parameters for simplified human PBPK models for caffeine, warfarin, omeprazole, metoprolol, and midazolam calculated from parameters in humanized mice, marmosets, cynomolgus monkey, dog, and minipig models.

probe drug	PBPK model	absorbed × intestinal availability, F_aF_g	absorption rate constant, k_a (1/h)	distribution volume, V₁ (L)	hepatic intrinsic clearance, CL_h,int, _{in vivo} (L/h)	hepatic clearance, CL_h (L/h)	AUC_last, ng h⁻¹ mL⁻¹
caffeine	human, from humanized mice	1	0.50	18.6	4.91	4.35	26200
	human, average (± SD)	1	0.97 (± 0.57)	58.1 (± 29.4)	7.25 (± 1.71)	4.83 (± 2.52)	16700 (± 6000)
	literature						21,300 (± 9,530)
S-warfarin	human, from humanized mice	1	7.51	5.90	2.54	0.259	17000
	human, average (± SD)	1	2.74 (± 3.03)	9.7 (± 4.4)	2.90 (± 2.41)	0.25 (± 0.26)	13900 (± 3380)
	literature						16,000 (± 4,340)
omeprazole	human, from humanized mice	1	2.84	77.2	2020	52.2	229
	human, average (± SD)	1	2.59 (± 1.84)	37.2 (± 26.9)	1340 (± 513)	40.9 (± 9.9)	407 (± 216)
	literature						368 (± 250)
metoprolol	human, from humanized mice	1	1.65	174	105	46.5	1300
	human, average (± SD)	1	0.91 (± 0.48)	200 (± 66)	178 (± 110)	55.9 (± 10.6)	939 (± 347)
	literature						449 (± 303)
midazolam	Human, from humanized mice	1	2.37	62	475	31.7	53.5
	Human, average (± SD)	1	1.00 (± 0.82)	71 (± 33)	827 (± 352)	41.5 (± 10.4)	37.5 (± 17.4)
	Literature						23.7 (± 8.0)

Estimates of human plasma concentrations of various P450 probes were based on non-human primates, dog, and minipig plasma data.^31–33 Average parameters for humans were calculated with human PBPK models based on five animal models. Values in parentheses are SD values. Literature values⁵⁷ are ±SD.