TABLE 5

Kinetic parameters for the initial uptake of pitavastatin, rosuvastatin, and pravastatin in human hepatocytes

Values are shown as the mean ± S.D.

Drug	Lot	V_max	K_m	V_max/K_m	PS_dif	K_p,uu,V0^{^d}	f_T,cell,V0^{^d}
		pmol/min/10⁶ Cells	μM	μL/min/10⁶ Cells	μL/min/10⁶ Cells
Pitavastatin	Hu8075^{^a}	403 ± 84	4.77 ± 1.80	84.5 ± 36.4	0.388 ± 0.912	219 ± 521	0.465 ± 1.110
	TFF^{^b}	148 ± 66.1	1.78 ± 1.04	83.1 ± 61.1	4.36 ± 0.70	20.1 ± 14.4	0.134 ± 0.096
Rosuvastatin	Hu8075^{^a}	198 ± 50	21.5 ± 7.8	9.21 ± 4.07	0.0462 ± 0.1547	200 ± 673	3.83 ± 12.91
	TFF^{^b}	23.0 ± 8.6	4.49 ± 1.72	5.12 ± 2.75	2.07 ± 0.279	3.47 ± 1.41	0.128 ± 0.053
Pravastatin	Hu8075^{^a}	93.8 ± 56.0	127 ± 81	0.739 ± 0.645	0.0137 ± 0.0922	54.8 ± 363.7	14.7 ± 97.5
	TFF			Not determined^{^c}

↵^a The initial uptake rate in isolated cryopreserved human hepatocytes (Lot Hu8075) was calculated from the uptake of [³H]pitavastatin, [³H]rosuvastatin, and [³H]pravastatin for 0.5–2.0 minutes. Kinetic parameters are obtained by fitting to the data at several concentrations (0.1, 0.3, 1, 3, 10, 30, and 100 µM for pitavastatin; 0.1, 0.3, 1, 3, 10, 30, and 300 µM for rosuvastatin; 1, 3, 100, and 300 µM for pravastatin; Supplemental Fig. 3, A–C) using eq. 4.
↵^b The initial uptake rate in pooled cryopreserved human hepatocytes from 20 mixed-sex donors (Lot TFF) was calculated from the uptake of [³H]pitavastatin and [³H]rosuvastatin for 0.5–1.5 minutes. Kinetic parameters are obtained by fitting to the data at several concentrations (0.1, 0.3, 1, 3, 10, 30, and 100 µM for pitavastatin; 0.1, 0.3, 1, 3, 10, 30, and 300 µM for rosuvastatin; Supplemental Fig. 3, D and E) using eq. 4.
↵^c Not determined in Lot TFF because a concentration (0.5–300 µM)-dependent saturation of the uptake of pravastatin was not observed clearly.
↵^d The K_p,uu,V0 and f_T,cell,V0 were calculated using eqs. 5 and 6, respectively. C/M ratios at 37°C (Table 4) were used for the calculation of the f_T,cell,V0.