TABLE 5.

Mean pharmacokinetic parameters for GS2 and GS-6620 following oral administration to pentagastrin-pretreated portal vein-cannulated male beagle dogs^d

Prodrug	Cmax portal (μM)	AUC0–t portal (μM · h)	Cmax jugular (μM)	AUC0–t jugular (μM · h)	Faa (%)	EHb (%)	Fc (%)
GS2	1.61 ± 0.35	1.77 ± 0.26	0.43 ± 0.09	0.44 ± 0.09	52	75	13
GS-6620	3.65 ± 0.86	1.68 ± 0.80	0.62 ± 0.43	0.33 ± 0.28	79	80	15

^aFraction absorbed (F_a) was calculated by comparing the dose-normalized portal vein exposure (AUC_0–t) following oral administration to the AUC_0–t observed following a 0.5-mg/kg intravenous infusion (30 min) of 0.34 ± 0.04 μM · h and 0.20 ± 0.04 μM · h for GS2 and GS-6620, respectively. Exposure values for intravenous infusion are the means ± SD (n = 3).

^bHepatic extraction (E_H) was calculated using the equation 100% × (AUC_0–t portal − AUC_0–t jugular)/AUC_0–t jugular.

^cOral bioavailability (F) was calculated by comparing the dose-normalized jugular vein AUC_0–t following oral administration to AUC_0–t observed following intravenous infusion.

^dGS2 was used at 5 mg/kg in solution, and GS-6620 was used at 5 mg/kg in suspension of micronized material.