Table 3.

Model predicted parameters describing CDFDA transport and hydrolysis, and CDF efflux transport across apical and basolateral membranes following apical or basolateral exposure to 5 μM CDFDA.

Parameter	Parameter Estimate (% RSE)		Bootstrap Analysis
	Apical Dosing	Basolateral Dosing	Apical Dosing	Basolateral Dosing
Clcdfda	0.004 (fixed)	0.004 (fixed)	----	----
Clhydrolysis	8.2 × 10−4 (<0.1)	1.5 × 10−3 (0.1)	1.0 × 10−2 (0.9 – 1.2 × 10−2)	1.6 × 10−3 (1.2 – 1.9 × 10−3)
Clcdf,ap	8.4 × 10−5 (<0.1)	8.5 × 10−5 (0.2)	2.2 × 10−5 (1.7 – 2.6 × 10−5)	8.3 × 10−5 (7.1 – 10.8 × 10−5)
Clcdf,bl	5.6 × 10−5 (0.1)	5.2 × 10−5 (0.2)	1.3 × 10−5 (1.2 – 1.4 × 10−5)	5.1 × 10−5 (3.8 – 6.7 × 10−5)
BOFVhydrolysis	11.0 (20.6)	34.0 (20.4)	7.3 (19.2)	31.4 (33.5)
BOFVClcdf,ap	12.2 (20.5)	13.6 (20.6)	2.9 (79.2)	14.5 (8.6)
BOFVClcdf,bl	11.2 (21.4)	24.0 (20.4)	7.5 (21.9)	24.4 (41.7)
RUVbl (proportional)	30.2 (13.7)	0.1 (160.0)	0.74 (0.67 – 0.94)	0.06 (0 – 0.21)
RUVcell (proportional)	0.2 (101.1)	0.02 (161.6)	2.0 (0.02 – 2.4)	7.3 (0 – 270)
RUVap (proportional)	0.01 (99.6)	10.3 (1.5)	7.1 (5.9 – 8.4)	9.4 (3.9 – 18.5)

Results are presented as the population parameter estimates (% RSE is the percent relative standard error of the population estimate). Clearance parameters have units of mL/min. Cl_cdfda, diffusional clearance of CDFDA; Cl_hydrolysis intracellular hydrolysis of CDFDA; Cl_cdf,ap, efflux clearance of CDF across the apical membrane; Cl_cdf,bl, efflux clearance of CDF across the basolateral membrane; BOFV, between occasion and filter variability; RUV, residual unexplained variability. BOFV and RUV results are expressed in percent. Apical, cell and basolateral compartment volumes were fixed to 0.5 mL, 0.0028 mL and 1.5 mL, respectively. Bootstrap analysis parameter estimates are expressed as median (5% and 95% boundaries of the 90% confidence interval), except for BOFV estimates, which are expressed as median (%RSE).