The pharmacokinetics of 1,2-diethyl-3-hydroxypyridin-4-one (CP94) in rats.

The pharmacokinetics of 1,2-diethyl-3-hydroxypyridin-4-one (CP94) and its 2-(1-hydroxyethyl) metabolite (metabolite A) were examined in male Wistar rats using a chronically cannulated conscious-rat model. Serial blood samples were assayed by a reversed phase HPLC method with UV detection. Following iv doses of 25, 50, and 100 mg/kg, the parent compound was eliminated from blood in a biexponential fashion with an average systemic clearance of 1.5 liters/hr/kg. The mean terminal elimination half-life was 2.02 hr and the mean volume of distribution at steady state was 2.69 liters/kg. The areas under the curve (AUCs) for the 25, 50, and 100 mg/kg iv doses were 15, 36, and 72 micrograms/ml/hr, respectively, suggesting that the disposition of CP94 in rats obeys linear kinetics. The oral bioavailability of CP94 (100 mg/kg) was about 53%. Peak blood concentration occurred at about 0.5 hr after oral administration. Following iv doses of CP94 at 25, 50, and 100 mg/kg, metabolite A peaked at about 0.75 hr.