Table 4.

Plasma and organ pharmacokinetic parameters of selpercatinib in female wild-type, Cyp3a^-/- and Cyp3aXAV mice over 8 h after oral administration of 10 mg/kg selpercatinib.

Parameter	Genotype
	Wild-Type	Cyp3a-/-	Cyp3aXAV
AUC0–8h, ng/mL*h	52,251 ± 6922	72,243 ± 5642 ***	45,755 ± 3460 ###
Fold change AUC0–8h	1.0	1.4	0.88
Cmax, ng/mL	8556 ± 1299	12,295 ± 1311 ***	9477 ± 548 ##
Tmax, h	1.5 ± 1.3	1.4 ± 1.3	0.29 ± 0.10 *#
Cbrain, ng/g	82.4 ± 16.8	86.2 ± 24.2	51.0 ± 15.2 *##
Fold change Cbrain	1.0	1.0	0.62
Brain-to-plasma ratio	0.021 ± 0.002	0.022 ± 0.002	0.022 ± 0.002
Fold change ratio	1.0	1.0	1.0
CLiver, ng/g	8255 ± 1615	7896 ± 1274	4386 ± 755 ***###
Fold change Cliver	1.0	1.0	0.53
Liver-to-plasma ratio	2.1 ± 0.3	2.1 ± 0.2	2.0 ± 0.2
Fold change ratio	1.0	1.0	1.0
CSI, ng/g	7302 ± 1116	6384 ± 930	5030 ± 347 ***#
Fold change CSI	1.0	0.87	0.69
SI-to-plasma ratio	1.9 ± 0.4	1.7 ± 0.3	2.3 ± 0.6
Fold change ratio	1.0	0.89	1.2
CSIC, ng/g	83,866 ± 51,955	44,922 ± 15,127	48,515 ± 13,654
Fold change CSIC	1.0	0.54	0.58
SIC-to-plasma ratio	20.0 ± 7.9	11.5 ± 3.3 *	22.3 ± 7.5 ##
Fold change ratio	1.0	0.58	1.1
SIC percentage of dose, %	2.5 ± 0.9	1.4 ± 0.6 *	1.5 ± 0.5
Fold change %	1.0	0.56	0.60

Data are given as mean ± S.D. (n = 6–7). AUC_0–8h, area under plasma concentration–time curve; C_max, maximum concentration in plasma; T_max, time point (h) of maximum plasma concentration; C_brain, brain concentration. C_liver, liver concentration; SI, small intestine (tissue); C_SI, small intestine tissue concentration; SIC, small intestine contents; C_SIC, small intestine contents concentration; *, p < 0.05; **, p < 0.01; ***, p < 0.001 compared to wild-type mice; #, p < 0.05; ##, p < 0.01; ###, p < 0.001 compared between Cyp3a^-/- and Cyp3aXAV mice. Statistical analysis was applied after log-transformation of linear data.