Table 7.

Tissue and plasma concentrations of ASV after PO dosing across species^a

Species (PO dose, mg/kg)b	Sample analyzed	C24 (nM)	T/P AUC ratio	Fold GT1a EC50c
Mouse (5)	Serum	<LLOQ
	Liver	714 ± 330d	>80e	179 (28)
Rat (15)	Plasma	38		9.5 (1.5)
	Liver	11,986	359	2,997 (461)
Dog (6)	Plasma	6		1.5 (0.2)
	Liver	2,541	40	635 (98)
	Spleen	<LLOQ	0.5
Monkey (10)	Plasma	<LLOQ		ND
	Liver	441	151	110 (17)
	Spleen	<LLOQ	ND

^aC₂₄, concentration at 24 h postdose; GT, genotype; L, liver; LLOQ, lower limit of quantification; ND, not determined; T, tissue; P, plasma.

^bMice (n = 3 per time point) were dosed at 5 mg/kg and monitored for 24 h, rats (n = 2 per time point) were dosed at 15 mg/kg PO and monitored for up to 72 h postdose, dogs (n = 1 per time point) were dosed at 6 mg/kg PO and monitored for up to 72 h, and monkeys (n = 1 or 2 per time point) were dosed at 10 mg/kg PO and monitored for up to 30 h postdose. Average values are shown for rats and monkeys, whereas only single values were obtained for dogs.

^cFold EC₅₀ multiples of ASV were calculated by dividing the C₂₄ value by the EC₅₀ for ASV in HCV genotype 1a replicons (EC₅₀ ≈ 4 nM). Values in parentheses represent a similar calculation using the ASV EC₅₀ in 40% human serum (EC₅₀ ≈ 26 nM).

^dAverage ± standard deviation.

^eLiver-to-serum ratio was determined.