TABLE 1.

Pharmacokinetic parameter values for NITD449 and its prodrug NITD203 observed following oral and intravenous administration to female CD-1 mice and female Wistar rats

Species	Compound	Dose(s) (mg/kg)	PK parametera value for indicated route
			Oral				Intravenousb
			Cmax (μM)	Tmax (h)	AUC∞ (μM/h)	F (%)	Vss (liters/kg)	CL (ml/min/kg)	t1/2 (h)
Mouse	NITD449e	25	0.27	1	0.42	1	0.26	21.88	1.31
	NITD449 from NITD203f	24.2,c 17.0d	6.01	0.08	12.57	32
Rat	NITD449e	24.8	0.27	0.17	3.15	2	2.71	8.98	8.33
	NITD449 from NITD203f	26.5, 18.7d	3.65	0.5	13.71	13
	NITD449 from NITD203g	84.1, 59.2d	14.2	0.5	33.45	10

^aC_max, maximum concentration of drug in plasma; T_max, time to maximum concentration of drug in plasma; AUC_∞, area under the curve extrapolated to infinity; V_ss, volume of distribution at steady state; CL, clearance; t_1/2, elimination half-life; F, oral bioavailability.

^bThe intravenous doses of NITD449 were 5mg/kg in the mouse and 5.9mg/kg in the rat.

^cThe administered dose of the prodrug NITD203 (mg/kg).

^dThe corresponding dose of the conversion product NITD449 (mg/kg).

^eThe solution formulation was 0.1 N HCl (1.5 equimolar amount) and 1 N NaOH (pH adjusted to 3.5), topped off with 100 mM citrate buffer (pH 3.5).

^fThe solution formulation was 10% ethanol, 30% polyethylene glycol 400 (PEG 400), and 60% of 5% dextrose in water (D5W).

^gThe solution formulation was 20% solutol HS15, 30% PEG 300, and 50% of 100 mM citrate buffer (pH 3).