TABLE 4

Scheme B: MRT_cell as functions of CL_int,sec, CL_d1, CL_d2, k_a, and nonlinear metabolism (K_m of 20 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	27.9^*	16.5	15.8	15.4	75.1^*	15.5^*	14.2	13.3
100	5	26.8^*	24.1	23.9	23.7	53.0^*	15.5^*	14.4	13.5
100	10	35.5^*	34.0	33.9	33.8	43.3^*	15.6^*	14.6	13.8
300	1	57.3^*	31.1	30.7	30.5	104^*	29.6	29.1	28.7
300	5	45.9^*	38.8	38.5	38.3	87.9^*	29.8	29.3	29.0
300	10	52.5^*	48.9	48.7	48.6	78.5^*	30.0	29.5	29.3
Basolateral Administration
100	1	136	22.2	21.0	20.2	134	20.1	18.9	18.0
100	5	145	30.8	29.3	28.4	134	20.4	19.2	18.3
100	10	156	41.3	39.6	38.6	134	20.8	19.5	18.7
300	1	138	46.0	45.4	44.9	136	43.7	43.1	42.7
300	5	149	55.0	54.2	53.7	136	44.0	43.4	43.0
300	10	162	64.9	63.8	63.2	137	44.5	43.8	43.4

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