TABLE 3

Scheme B: MRT_cell as functions of CL_int,sec, CL_d1 CL_d2, k_a, and nonlinear metabolism (K_m of 10 μM and V_max of 10 nmol/min). Initial drug concentrations of 100 and 300 μM were used; eq. 2 was used to estimate the MRT.

C_ln	CL_int,sec	MRT_cell (min) at k_a = 1 min^-1							MRT_cell (min) at k_a = 30 min^-1
C_ln	CL_int,sec			CL_d1 = CL_d2 (0.02 ml/min)	CL_d1 = CL_d2 (0.5 ml/min)	CL_d1 = CL_d2 (1 ml/min)	CL_d1 = CL_d2 (5 ml/min)	CL_d1 = CL_d2 (0.02 ml/min)	CL_d1 = CL_d2 (0.5 ml/min)	CL_d1 = CL_d2 (1 ml/min)	CL_d1 = CL_d2 (5 ml/min)
μM	ml/min
Apical Administration
100	1	24.3^*	12.7	12.1	11.8	72.6^*	12.4^*	11.4	10.7
100	5	19.0^*	16.3	16.1	15.9	49.6^*	12.4^*	11.4	10.8
100	10	22.7^*	21.3	21.2	21.1	40.5^*	12.4^*	11.5	10.9
300	1	53.7^*	27.4	27.1	26.9	101^*	26.6	26.0	25.4
300	5	38.6^*	31.1	30.9	30.8	84.6^*	26.7	26.2	25.6
300	10	39.7^*	35.9	35.7	35.6	77.1^*	26.8	26.3	25.8
Basolateral Administration
100	1	132	17.9	17.0	16.4	131	16.9	16.0	15.6
100	5	136	22.5	21.4	20.7	131	17.1	16.2	15.7
100	10	142	28.0	26.6	25.9	131	17.2	16.3	15.9
300	1	133	41.1	40.5	40.1	132	39.8	38.8	37.8
300	5	139	46.3	45.7	45.4	132	39.9	39.0	38.1
300	10	145	52.2	51.5	51.1	132	40.2	39.3	38.5

↵* Deviating trend: increasing values of CL_int,sec failed to increase the MRT