TABLE 1.

Population PK parameter estimates

Parameter	Mean Parameter Estimate	S.E	P Value
F_pop	0.175	0.0072
θ_Pgp KO	0.227	0.062	0.00028
θ_dKO	0.514	0.062	<1e−10
Tk0_pop (1/h)	0.104	0.0092
F2_pop	1 fixed	N.E.
ka_pop (1/h)	19.1	1.6
V1_pop (1/kg)	9.32	0.35
CL_pop (1/h per kilogram)	20.2	0.72
ω_BSV
F	0.0276	0.077
Tk0	0.32	0.077
F2	N.E.	N.E.
ka	0.091	0.14
V1	0.0857	0.061
CL	0.0781	0.056
σ-RUV
Proportional	0.341	0.022
F_(WT and Bcrp KO)	0.175	0.0072
F_(Pgp KO)	0.22	0.011
F_(dKO)	0.293	0.015

CL_pop, population mean clearance; F, oral bioavailability; F_pop, population mean oral bioavailability; F2_pop, population mean intraperitoneal bioavailability (which was assumed to be 1); k_a_pop, population mean first-order absorption rate constant for the intraperitoneal route; N.E. : Not Estimated., ; ω_BSV, between-subject variability; σ-RUV, residual unexplained variability; θ_Pgp KO and θ_dKO, estimated coefficient of the effect of categorical covariate Pgp KO and dKO on the oral bioavailability; Tk0_pop, population mean oral zero-order absorption rate constant; V1_pop, population mean volume of distribution.