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), 3156.13 μg/L; A UC, 46281.5 μg/L/h) by 3 folds in rats compared with the administration of gefitinib alone (C (max), 1352.07 μg/L; AUC, 11823.7 μg/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.