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
Parameter	Estimate	CV	Estimate	CV
	h⁻¹	%	h⁻¹	%
k_{P_net uptake}	58	88	13	23
k_P→M1	N.A.^b	N.A.	3.8	7
k_{M1_reuptake}	N.A.	N.A.	96	55
k_{M1_efflux}	N.A.	N.A.	330	62
k_P→M3	1.7	6	N.A.	N.A.
k_M1→M3	N.A.	N.A.	108	20
k_{M3_reuptake}	13	69	11	33
k_{M3_efflux}	0.31	72	0.20	29
k_{M3_bile}	0.096	11	0.42	14
k_M3→A	0.43	8	1.5	12
k_{A_reuptake}	2.7	>100	3.3	>100
k_{A_efflux}	0.0065	>100	0.028	>100
k_{A_net efflux}^{^a}	0.0021	14	0.012	51
k_{A_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}.