TABLE 5.

Kinetic parameters, generated from model 1, associated with disposition of prodrugs (pafuramidine and CPD-0868) and derived metabolites in day-4 rat SCH

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. S2 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	0.30	7	0.40	4
kP→M1	N.A.b	N.A.	67	37
kM1_reuptake	N.A.	N.A.	3.5	29
kM1_efflux	N.A.	N.A.	71	42
kP→M3	1.3	26	N.A.	N.A.
kM1→M3	N.A.	N.A.	12	40
kM3_reuptake	0.080	90	0.15	30
kM3_efflux	N.A.	N.A.	0.35	27
kM3_bile	N.A.	N.A.	0.050	55
kM3→A	0.46	16	0.66	15
kA_reuptake	0.83	>100	0.27	>100
kA_efflux	0.0080	>100	0.015	>100
kA_net effluxa	0.00076	>100	0.0046	27
kA_bile	N.A.	N.A.	N.A.	N.A.

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}.