Sprague dawley jugular canulated rats

Test compound was administered to Sprague-Dawley jugular canulated rats (Charles River) by either oral gavage or IV injection followed by blood sampling from the jugular vein at 5, 15, 30, 60, 90, 120, 240, 360, 480, 720 and 1440 min. The oral dose was administered to each rat at 20 mg/kg at time = 0 in a 1 mL volume of dosing solution (7% Tween 80, 3% EtOH, 5% DMSO, 09.% saline.) IV injections were administered at 5 mg/kg from time = 0 to 3 minutes in a 1 mL volume of dosing solution, and blood was sampled at the same time points via the jugular vein. Experiments were performed with groups of 2 rats each for the oral and IV dosing. Plasma was separated and extracted with acetonitrile for measurements of compound concentrations by liquid chromatography/tandem mass spectrometry. PK calculation were performed using Phoenix WinNonlin software (Pharsight).

Test compound was administered to Sprague-Dawley jugular canulated rats (Charles River) by either oral gavage or IV injection followed by blood sampling from the jugular vein at designated time points (performed under IACUC protocol number 2145-01 (UW, Seattle)). The oral dose was administered to each rat at 20 mg/kg for compound 32 and 5 mg/kg for compound 33 at time = 0 in a 1 mL volume of dosing solution (7% Tween 80, 3% EtOH, 5% DMSO, 0.9% saline.) IV injections were administered at 5 mg/kg from time = 0 to 3 minutes in a 1 mL volume of dosing solution, and blood was sampled at the same time points via the jugular vein. Experiments were performed with groups of 2 rats each for the oral and IV dosing. Plasma was separated and extracted with acetonitrile and quantified by LC/MS analysis. PK calculations were performed using Phoenix WinNonlin software (Pharsight).