TABLE 5.

Pharmacokinetic parameters of compound 17 dosed orally in solid dispersion formulation to Beagle dogs^a

Parameterb	Value for the parameter at the indicated dose (mg/kg) of:c
	Intact prodrug				Nucleoside 7				Triphosphate 6
	10	30	100	300	10	30	100	300	10	30
Cmax (μM)	1.9	4.6	17.3	24.9	0.5	1.3	3.4	7.5	13.1	22.3
Tmax (h)	0.5	0.5	0.7	0.7	2.3	3.0	3.0	3.0	32d	9.3d
AUClast (μM⋅h)	1.9	5.6	33.6	72.6	7.2	17.0	46.4	130.6	957.6	1879.9
t1/2 (h)	0.4	0.7	1.1	4.7	8.9	26.9	8.6	31.1	86.6	86.6

^aCompound 17 was dosed orally at 10, 30, 100, and 300 mg/kg in solid dispersion formulation to Beagle dogs (n = 3).

^bC_max, maximum concentration; T_max, time to reach maximum concentration; AUC_last, area under the concentration-time curve (t = 0 until the last measurable concentration; for intact prodrug and nucleoside, t = 0 up to 24 h [Fig. 7A and B]; for triphosphate, t = 0 to 168 hours); t_1/2, half-life.

^cIntact prodrug and major metabolite 7 were measured in plasma from all dose groups. Triphosphate 6 was measured in PBMCs only from the 10- and 30-mg/kg dose groups.

^dHigh interanimal variability observed (Fig. 7C).