. 2020 May 26;13(6):1199–1207. doi: 10.1111/cts.12804

Table 2.

Predicted CL_h using the canonical and new approaches and measured in vivo CL_h

Drugs	Major CYP	f _u‐blood ^a	f _u‐mic ^a	Predicted CL_h (mL/min)							In vivo ${CL}_{h}$ (mL/min) ^a ^, ^c
				Dispersion model		Well‐stirred model			Parallel tube model
				Canonical	New		Canonical	New	Canonical	New
Coumarin	2A6	0.02	0.99 ^b	971 ~ 1,357	547 ~ 718		814 ~ 1,151	508 ~ 622	1,048 ~ 1,418	606 ~ 765	625
Paclitaxel	2C8	0.12	0.66	215 ~ 484	187 ~ 364		204 ~ 436	179 ~ 335	219 ~ 507	190 ~ 376	141
Propafenone	2D6	0.06	0.26	1,329 ~ 1,444	822 ~ 919		1,119 ~ 1,320	701 ~ 775	1,400 ~ 1,449	881 ~ 990	400
Midazolam	3A4	0.07	0.54	1,260 ~ 1,436	1,060 ~ 1,256		1,050 ~ 1,288	884 ~ 1,046	1,345 ~ 1,449	1,146 ~ 1,341	429
Indinavir		0.40	0.97	1,190 ~ 1,425	1,028 ~ 1,264		988 ~ 1,256	859 ~ 1,054	1,279 ~ 1,447	1,111 ~ 1,349	624
Cyclosporine		0.07	0.37	281 ~ 669	236 ~ 462		263 ~ 584	223 ~ 418	288 ~ 711	241 ~ 482	209
Saquinavir		0.02	0.58	1,292 ~ 1,440	876 ~ 1,005		1,081 ~ 1,303	742 ~ 841	1,372 ~ 1,449	942 ~ 1,085	452
Cabazitaxel		0.1	0.42 ^b	1,051 ~ 1,389	855 ~ 1,120		876 ~ 1,193	726 ~ 931	1,135 ~ 1,435	919 ~ 1,209	790
Docetaxel		0.07	0.01 ^b	1,286 ~ 1,440	1,024 ~ 1,194		1,075 ~ 1,300	855 ~ 991	1,367 ~ 1,449	1,106 ~ 1,283	504
Valspodar		0.02	0.07 ^b	721 ~ 1,215	467 ~ 650		624 ~ 1,010	422 ~ 568	769 ~ 1,304	488 ~ 689	182
Felodipine		0.01	0.08	1,179 ~ 1,423	1,042 ~ 1,289		979 ~ 1,251	869 ~ 1,077	1,269 ~ 1,446	1,125 ~ 1,369	829

CL_h, hepatic clearance; f _u‐blood, drugs unbound fraction in blood; f _u‐mic, drugs unbound fraction in microsome.

^{^a}

See Supplementary Excel File for references of f _u‐blood, f _u‐mic and in vivo ${CL}_{h}$ .

^{^b}

f _u‐mic of coumarin, cabazitaxel, docetaxel, and valspodar were estimated using this equation, $\frac{1}{C \times 10^{0.56 \log P / D - 1.41} + 1}$ as they have not been measured. ¹⁷ Microsomal protein concentrations (C) for coumarin, cabazitaxel, docetaxel, and valspodar were 0.03, 0.5, 1, and 1 mg/mL, respectively. Log P = 1.39 for coumarin and Log D _7.4 = 3.3 for cabazitaxel were calculated using ACD/Labs Percepta Platform—PhysChem Module. Log D _7.4 = 6.5 and 4.5 for docetaxel and valspodar were referenced by Bu, 2006.

^{^c}

See Methods and Supplementary Excel File for detailed derivation of in vivo CL_h.