Table 1.

Estimated ${\text{CL}}_{\text{int}}^{\text{liver}}$ using the canonical and new approaches

Drugs a	K M (µM) b	Vmax (pmol∙min−1∙pmol CYP−1) c , d	Major CYP	CYP abundance in HLM (pmol/mg)	${\tilde{E}}_{\mathrm{T}}$ (µmol) c,d	E T (µM) e	${\text{CL}}_{\text{int}}^{\text{liver}}$ (mL/min)
							Canonical f	New g
Coumarin	0.75	39.2	2A6	30.7 ~ 56.2 9 , 22	1.77 ~ 5.31	1.03 ~ 3.10	92,457 ~ 277,683	38,924 ~ 54,122
Paclitaxel	5.5	4.64	2C8	26.9 ~ 43.0 9 , 22	1.55 ~ 4.06	0.90 ~ 2.37	1,308 ~ 3,429	1,123 ~ 2,396
Propafenone	0.12	4.83	2D6	9.34 ~ 17.2 11 , 22	0.54 ~ 1.63	0.31 ~ 0.95	21,626 ~ 65,339	5,982 ~ 7,340
Midazolam	1.6	24.4	3A4	32.6 ~ 60.4 11 , 22	1.88 ~ 5.71	1.10 ~ 3.33	28,630 ~ 87,025	16,995 ~ 28,246
Indinavir	2.31	9.28					7,535 ~ 22,905	5,112 ~ 9,382
Cyclosporine	5	4.44					1,666 ~ 5,063	1,366 ~ 3,039
Saquinavir	0.61	40.4					124,247 ~ 377,671	44,443 ~ 58,479
Cabazitaxel	2.1	9.5					8,499 ~ 25,835	5,586 ~ 9,992
Docetaxel	1.1	0.20					348 ~ 1,059	175 ~ 263
Valspodar	1.3	2.49					3,588 ~ 10,906	1,947 ~ 3,062
Felodipine	2.81	36.2					24,156 ~ 73,427	17,381 ~ 33,606

${\text{CL}}_{\text{int}}^{\text{liver}}$, intrinsic clearance of the liver; HLM, human liver microsome; K _M, Michaelis‐Menten constant; V _max, maximal rate of metabolism.

^aSee Methods for the criteria for the drug selections.

^bSee Supplementary Excel File for references of K _M and V _max values.

^cObtained by dividing the measured rate per mg of the microsomes by the rate per pmol CYP with mean population abundance of CYP (pmol/mg): CYP2A6 (45.37), CYP2C8 (32.30), CYP2D6 (13.26), and CYP3A4 (45.07). ⁹ , ¹⁰ , ¹¹ , ²²

^dThe hepatic CYP amount is estimated by multiplying CYP abundance in HLM (pmol/mg) by MPPGL and liver weight (see Methods for details).

^eThe hepatic CYP concentration is estimated based on the assumption that CYPs are evenly distributed (see Methods for details).

^fCanonical ${\text{CL}}_{\text{int}}^{\text{liver}}=\frac{V_{max}}{K_{\mathrm{M}}}·{\tilde{E}}_{\mathrm{T}}$.

^gNew ${\text{CL}}_{\text{int}}^{\text{liver}}=\frac{V_{max}}{K_{\mathrm{M}}+E_{\mathrm{T}}}·{\tilde{E}}_{\mathrm{T}}=\text{Canonical}{\text{CL}}_{\text{int}}^{\text{liver}}·\frac{K_{\mathrm{M}}}{K_{\mathrm{M}}+E_{\mathrm{T}}}$. See Supplementary Excel File for detailed calculation.