Table 3.

Simulation of renal clearance of para‐aminohippuric acid (PAH) and cimetidine in the presence and absence of active secretion clearances. The renal clearances were simulated as described in Methods section and Supplementary Materials using collected permeability data in Caco‐2 cells, plasma unbound fraction (f _u,p), active secretion clearance at apical side of each of the three subsegments of proximal tubule CL_api,scr and active secretion clearance at basolateral side of each of the three subsegments of proximal tubule CL_bsl,scr. The tubular subsegment for secretion clearance indicates the specific subsegment in which the secretion clearance was incorporated. Secretion clearances were set as 0 in all other subsegments

f u,p	Caco‐2 permeability (10‐6 cm/s)	CLapi,scr (l/h)	CLbsl,scr (l/h)	Tubular subsegment for secretion clearance	Observed CLr (ml/min)	Simulated CLr (ml/min)	Fold difference (simulated/observed)
Para‐aminohippuric acid
1	0.72	0	0		550	93.9	0.17
		7.43	295	Each subsegment		812	1.48
		22.3	884	1st subsegment		734	1.33
		22.3	884	2nd subsegment		746	1.36
		22.3	884	3rd subsegment		770	1.40
Cimetidine
0.8	1.37	0	0		543	90.6	0.17
		10.6	13.5	Each subsegment		427	0.79
		31.8	40.5	1st subsegment		383	0.71
		31.8	40.5	2nd subsegment		387	0.71
		31.8	40.5	3rd subsegment		393	0.72