The pharmacokinetic profile of LEO 134310 was determined in rat (male Sprague Dawley) and dog (female Beagle) after intravenous (i.v.) injection at 1 mg/kg. LEO 134310 was administered in isotonic cyclodextrin solution at 0.5 mg/mL (0.1% Citrate buffer pH 4, 20% hydroxy-propyl-β-cyclodextrin in 0.2% NaCl). The i.v. dose was given as a bolus in rats and as a slow injection over 2 min in dogs. The dosing volume was 2 mL/kg. Blood was immediately diluted after sampling in an inhibitory cocktail containing acetylcholinesterase inhibitor Dichlorvos [1 mg/mL in an 8 mg/mL K2EDTA solution in phosphate buffer (PBS)] and samples were stored at − 80 °C until analysis. Samples were analyzed by LC–MS/MS using an API 5500/API 6500 QTRAP mass spectrometer. Pharmacokinetic parameters were derived from a non-compartment model in Phoenix64 (Pharsight, Certara).
To evaluate allometric scaling, actual clearance in dog and man were extracted from the literature for 6 ester drugs27 (link)–38 (link).
To evaluate allometric scaling, actual clearance in dog and man were extracted from the literature for 6 ester drugs27 (link)–38 (link).