TABLE 5

Scheme B: MRT_cell as functions of CL_int,sec, CL_d1, CL_d2, k_a, and nonlinear metabolism (K_m of 50 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	38.7	27.4	26.9	26.5	80.2^*	24.1	22.6	21.3
100	5	50.0	47.0	46.9	46.7	61.3^*	24.3	23.1	22.0
100	10	74.0	72.0	71.9	71.8	51.0^*	24.7	23.7	22.8
300	1	67.5	42.2	41.6	41.2	112^*	38.0	36.9	36.0
300	5	68.8	61.9	61.6	61.4	96.6^*	38.5	37.5	36.7
300	10	90.8	86.9	86.8	86.7	85.6^*	39.1	38.3	37.5
Basolateral Administration
100	1	148	33.9	32.3	31.2	143	28.9	27.4	26.3
100	5	170	54.5	52.6	51.4	144	29.6	28.0	26.9
100	10	197	79.9	77.9	76.6	145	30.4	28.9	27.8
300	1	153	57.8	56.9	56.3	147	53.1	52.3	51.7
300	5	178	78.3	77.0	76.2	148	53.7	52.9	52.3
300	10	208	104	102	101	149	54.5	53.7	53.2

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