Studies on Pharmacokinetics and Liver Microsome Metabolism of Nuciferine in Different Species of Animals

Abstract

This study aimed to compare the characteristics of pharmacokinetics and liver microsome metabolism among different species of animals including rabbit, rat and mouse and healthy New Zealand white rabbits, SPF Sprague Dawley (SD) rats and ICR mice were given intraperitoneal injection of nuciferine at a dose of 50 mg per kg body weight. Blood samples were collected via caudal vein after administration and nuciferine concentrations in different points were determined by the method of HPLC-UV. Then the plasma concentration-time curves were drawn and the pharmacokinetics parameters were calculated by DAS 3.0 software. Besides, liver microsome from rabbit, rats and mice were prepared to study the metabolism of nuciferine in vitro. These results showed that nuciferine fitted two-compartment model in rabbits and rats and one-compartment model in mice. The calculated results of pharmacokinetics parameters showed that the fast absorption of nuciferine exhibited in rabbits, rats and mice, while the elimination was relatively slow. Compared with rabbits and rats, the nuciferine elimination was fastest in mice. The Km value of nuciferine metabolism in vitro was least in mice liver microsome, which suggested that the fastest metabolism of nuciferine existed in mice liver. Therefore, the pharmacokinetics characteristics of nuciferine in different species were significantly different, the elimination of nuciferine is the fastest in mice and the slowest in rabbits, which was in line with the in vitro metabolism trends by liver microsome from different species.