Effect of Single-Dose and Short-Term Administration of Si Jun Zi Tang on the Pharmacokinetics of Gefitinib in Rats

Abstract

Background. Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula that has been described for approximately one thousand years, is often prescribed for cancer patients as a complementary therapy in China. However, the mechanism by which Si Jun Zi Tang enhances the efficacy of gefitinib is unclear. Methods. We investigated how Si Jun Zi Tang affected the pharmacokinetics of gefitinib in rats. A rapid, specific, and reliable ultra-performance liquid chromatography method with mass spectrometry was established to determine the plasma concentration of gefitinib. Results. The results showed that a single intragastrically administered dose of Si Jun Zi Tang increased the pharmacokinetic parameters of gefitinib (C_max, 3156.13μg/L; A UC, 46281.5μg/L/h) by 3 folds in rats compared with the administration of gefitinib alone (C_max, 1352.07μg/L; AUC, 11823.7μg/L/h). Si Jun Zi Tang could also alter the pharmacokinetics of gefitinib by prolonging the time to reach C_max. Conclusions. Potential pharmacokinetic interactions between gefitinib and SJZ were evaluated, and SJZ extended T_max and T1/2 and increased the C_max and AUC of gefitinib. Long-term administration of gefitinib in combination with Si Jun Zi Tang would improve the efficacy of gefitinib.