TABLE 4.

Data summary: comparison of the Kp estimates among different routes of administration, including a single intravenous bolus (3 mg/kg, i.v.; N = 3 to 4 at each time point), an oral dose (30 mg/kg, PO; N = 4 at each time point), or a continuous steady-state intraperitoneal infusion (40 µg/h, i.p.; N = 4 in each genotype)

Data are presented as the mean. Data for the wild-type genotype after administration of a single oral dose were previously reported (Laramy et al., 2017) and are included in this present study to compare with the three other genotypes that lack efflux transporters.

Genotype	Kpa					DAb
	i.v.		PO		i.p.	i.v.		PO		i.p.
	A	B	A	B	C	A	B	A	B	C
FVB wild-type	1.0	1.7	0.82	0.87	1.0	—	—	—	—	—
Bcrp1(−/−)	—	—	1.3	1.6	1.8	—	—	1.6	1.9	1.7
Mdr1a/b(−/−)	—	—	3.6	4.9	3.8	—	—	4.4	5.7	3.7
Mdr1a/b(−/−)	—	—	—	—	—	—	—	—	—	—
Bcrp1(−/−)	10.0	11.6	14.2	12.7	15.6	9.9	6.9	17.3	14.6	15.0

^aMethod A, Kp = [AUC_{(0→∞),brain}]/[AUC_{(0→∞),plasma}]; Method B, Kp = Transient steady-state concentration ratio = C_max,brain/Corresponding plasma concentration at that time point (C_p,tss); Method C, Kp = Steady-state brain-to-plasma concentration ratio.

^bKp,knockout/Kp,wild-type.