TABLE 2.

Kinetic parameters, generated from model 1, associated with the disposition of prodrugs (pafuramidine and CPD-0868) and derived metabolites in rat isolated perfused livers

Kinetic parameters are defined in the legend to Fig. 2. No discernable correlation between parameters was observed by evaluation of the correlation matrix (absolute correlation value ≤0.5). See Supplemental Fig. S1 for the plot of weighted residual vs. time data.

Parameter	Pafuramidine/Metabolites		CPD-0868 / Metabolites
	Estimate	CV	Estimate	CV
	h−1	%	h−1	%
kP_net uptake	58	88	13	23
kP→M1	N.A.b	N.A.	3.8	7
kM1_reuptake	N.A.	N.A.	96	55
kM1_efflux	N.A.	N.A.	330	62
kP→M3	1.7	6	N.A.	N.A.
kM1→M3	N.A.	N.A.	108	20
kM3_reuptake	13	69	11	33
kM3_efflux	0.31	72	0.20	29
kM3_bile	0.096	11	0.42	14
kM3→A	0.43	8	1.5	12
kA_reuptake	2.7	>100	3.3	>100
kA_efflux	0.0065	>100	0.028	>100
kA_net effluxa	0.0021	14	0.012	51
kA_bile	0.020	48	0.0084	61

N.A., not applicable.

^a Because of the high variability associated with the parameter estimates for k_A,reuptake and k_{A_efflux}, model 1 was modified to include a net efflux term, k_{A_net efflux}.