TABLE 6

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 50 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	8.49	6.72	6.38	5.98	25.1^*	8.22^*	6.18^*	4.62
100	5	11.0	10.5	10.4	10.2	17.8^*	7.52^*	6.15^*	4.74
100	10	15.8	15.5	15.4	15.3	13.8^*	7.05^*	6.08^*	4.90
300	1	16.6^*	9.82	9.25	8.85	49.2^*	10.1^*	8.62	7.60
300	5	15.0^*	13.4	13.2	13.0	37.7^*	9.87^*	8.66	7.74
300	10	19.2^*	18.4	18.3	18.2	29.9^*	9.75^*	8.72	7.91
Basolateral Administration
100	1	132	10.1	8.05	6.71	131	9.01	6.99	5.59
100	5	136	14.4	12.3	11.0	131	9.10	7.10	5.72
100	10	141	19.6	17.4	16.1	131	9.24	7.25	5.90
300	1	132	13.7	12.4	11.7	131	12.6	11.4	10.7
300	5	136	18.2	16.6	15.8	131	12.7	11.5	10.8
300	10	141	23.6	21.9	20.9	131	12.9	11.7	10.9

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