Extent of plasma protein binding of amphetamine in different species

Abstract

The extent of plasma protein binding of amphetamine in different species was determined in vitro by the equilibrium dialysis technique using 3 H-d- amphetamine sulphate and liquid scintillation counting. The per cent of amphetamine bound to plasma proteins was independent of drug concentration within the range of concentrations studied, that is 2·5 × 10 −7M to 4·0 × 10 −6 M. Protein binding was determined in pony, goat, swine, dog, cat, monkey, rabbit, opossum, rat, mouse, human and chicken plasmas at a drug concentration of 1·0 × 10 −6 M. The extent of binding was less than 45 per cent in all species but varied significantly among species (F-test, P < 0·01). Protein binding of this base appears to be associated with plasma albumin; there was no binding to 3 per cent equine or procine gamma globulin or to 2 per cent ovalbumin. The extent of protein binding (mean ± S.E.) in intact (23·1% ± 1·7) and nephrectomized uremie (24·3% ± 1·5) dogs was not significantly different. The non-protein bound drug appeared to diffuse freely into cerebrospinal and ocular fluids. The extent of protein binding was independent of drug concentration, similar in normal and uremie plasmas and significantly different among several species. These properties pose the interesting question as to the nature of the binding.