A phase 1b study of Selumetinib in combination with Cisplatin and Gemcitabine in advanced or metastatic biliary tract cancer: the ABC-04 study

Table 3 Pharmacokinetic parameters of selumetinib, by treatment combinations (75 mg bd)

Compound	PK Parameters^a	N^b	Sel + CisGem	Selumetinib alone	Sel vs Sel + CisGem Effect (90 % CI)^e
Selumetinib	AUC(0-t) (ng-hr/mL)	11	5304.37	4757.16	1.12 (0.95 to 1.30)
	AUC(0-∞) (ng-hr/mL)^c	11	6286.25	5653.31	1.11 (0.95 to 1.30)
	Cmax (ng/mL)	11	1725.64	1331.33	1.30 (0.91 to 1.85)
	Tmax (hours)^d	11	1.50	1.55	0 (−1.09 to 0 .57)
N-desmethyl selumetinib	AUC(0-t) (ng-hr/mL)	11	216.83	347.26	0.62 (0.43 to 0.91)
	AUC(0-∞) (ng-hr/mL)^c	11	277.55	452.88	0.61 (0.42 to 0.89)
	Cmax (ng/mL)	11	48.41	77.16	0.63 (0.43 to 0.91)
	Tmax (hours)^d	11	1.62	2.00	0 (−1.13 to 0 .50)

^aAnalysis used the actual time points when PK samples were collected. PK time point 0 corresponded to the time selumetinib was administered. Missing times of selumetinib dose administration were imputed from the non-missing time points. Missing concentrations for selumetinib and N-desmethyl selumetinib were estimated using linear interpolation
^bOf 12 patients, 11 were evaluable for PK analysis. Patients evaluable for PK analysis included the patients for whom a PK parameter could be imputed
^cLog linear models were used to extrapolate AUC (0-∞) using the last three measurements
^dTmax is expressed in terms of medians
^eRatio of geometric means between selumetinib and selumetinib + CisGem for AUC(0-t), AUC(0-∞) and Cmax. Rank-based difference in paired medians for Tmax

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