Sex dependent pharmacokinetics, tissue distribution and excretion of peimine and peiminine in rats assessed by liquid chromatography–tandem mass spectrometry

Abstract: Ethnopharmacological relevance: Fritillaria thunbergii Miq. has been traditionally used in China as antitussive and expectorant herbs, and newly used in the clinical treatment of leukemia in recent years. Aim: To investigate whether gender exerted a significant influence on the pharmacokinetics, tissue distribution and excretion of peimine and peiminine in Sprague-Dawley rats who were given a single oral administration of 4.25g/kg Fritillaria thunbergii Miq. extract. Materials and methods: Sprague-Dawley rats were assigned into two groups based on the gender and orally administered 4.25g/kg Fritillaria thunbergii Miq. extract for each individual pharmacokinetics, tissue distribution and excretion study. Results: Compared with female rats, peimine and peiminine were eliminated slowly from male rat plasma, and significant gender-related differences were observed in the pharmacokinetic parameters. Drug blood and tissue levels in male rats were significantly higher than the female counterparts except for several tissues, such as fat, muscle and skin. Gender also exerted a significant influence on the urine excretion but such effect was not observed in the feces excretion study. Conclusions: Gender exerted a significant influence on the pharmacokinetics, tissue distribution and urine excretion of peimine and peiminine. It is assumed that the sex-associated differences of peimine and peiminine in rats might be mainly result from sex-dependent expression and activity of drug metabolism enzymes and P-glycoprotein. [Copyright &y& Elsevier]