Gender-dependent pharmacokinetics of lignans in rats after single and multiple oral administration of Schisandra chinensis extract

Ethnopharmacological relevance: Schisandra chinensis (S. chinensis), a traditional Chinese medicine, has been widely used as sedatives and tonics in clinic. Schisandra lignans are believed to be the major bioactive components in S. chinensis. However, there is a lack of information about the effects of gender and repeated-dose on the pharmacokinetic properties of the schisandra lignans. Aim of the study: The study was performed to investigate the influence of gender on the pharmacokinetics of schisandra lignans after administration of S. chinensis extract and to compare their pharmacokinetic behaviors between single and multiple administration. Materials and methods: Two groups of rats (half male and half female) were received a single dose or multiple doses of S. chinensis extract, respectively. A liquid chromatography-tandem mass spectrometry method was developed and validated to determine the plasma concentrations of schisandra lignans. Results: The pharmacokinetic parameters of schisandrin, schisandrol B, deoxyschisandrin, gamma-schisandrin and schisantherin A were significantly different by gender difference. The t(1/2) of all the tested schisandra lignans in female rats were 2-9 times longer than the corresponding values in male rats. The C-max and AUC(0-t) of these schisandra lignans except schisantherin A in female rats were 5-50 times higher than those in male rats. The pharmacokinetic profiles of schisandrin, schisandrol B, deoxyschisandrin and schisantherin A in both gender rats after multiple doses were similar to the corresponding profile after single dose. Conclusion: All the tested schisandra lignans showed slower elimination and higher bioavailability in female rats after single or multiple administration of S. chinensis extract compared with male rats. Their pharmacokinetic profiles were not affected by repeated-dose except gamma-schisandrin, which was eliminated more slowly in female rats after multiple administration. (C) 2013 Elsevier Ireland Ltd. All rights reserved.