A Comparative Study of the Pharmacokinetics of Amphetamine

Abstract

Summary A similar dose (0·66 mg/kg) of dl-amphetamine sulphate was administered intravenously to healthy animals from each of 6 domesticated mammalian species and chickens. The concentration of amphetamine in plasma was measured by chromatography. The trichlor-acetautide derivative of amphetamine was chrontatographed on 3% OV-1 and detected by electron capture. Distribution equilibrium was rapidly attained and elimination followed first-order kinetics. Plasma half-lives of 0·62, 1·05, 1·39, 1·40, 2·27, 4·50 and 6·53 h were found in goats, swine, ponies, rabbits, chickens, dogs and cats, respectively. Sex difference in persistence of the drug was not observed in any species studied. The extent of plasma protein binding (in vitro) was determined by the equilibrium dialysis technique using 3H-d-ampltetamine sulphate and liquid scintillation counting. Extent of protein binding was independent of drug concentration and varied significantly among species. The apparent specific volumes of distribution, corrected for extent of plasma protein binding, were laroc (>2·0 l/kg) in all species; this indicated extensive tissue distribution and sequestration of the druo. A relationship appeared to exist between dietary habit and elimination of amphetamine. Elimination was significantly slower in carnivorous species than in the herbivorous and omnivorous species studied.