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 (Cmax, 3156.13 μg/L; A UC, 46281.5 μg/L/h) by 3 folds in rats compared with the administration of gefitinib alone (Cmax, 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 Cmax. Conclusions Potential pharmacokinetic interactions between gefitinib and SJZ were evaluated, and SJZ extended Tmax and T1/2 and increased the Cmax and AUC of gefitinib. Long-term administration of gefitinib in combination with Si Jun Zi Tang would improve the efficacy of gefitinib.
Highlights
Gefitinib is a selective small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is approved for the treatment of advanced non-small-cell lung cancer (NSCLC) with mutations of EGFR that are sensitive to gefitinib [1, 2]
Gefitinib is metabolized in the liver by cytochrome P450 (CYP) enzymes, mainly CYP3A4 [3]. us, it is susceptible to drug-drug interactions with any coadministered drug, and it has been known to be an inhibitor or inducer of CYP450 enzymes [3,4,5]
Mass Method Development. e mass spectrometric parameters were optimized with the corresponding standard solutions. e final analysis was conducted in positive ionization mode since it gave a good response to gefitinib and internal standard (IS), which was consistent with previous reports [1, 5, 12]
Summary
Gefitinib is a selective small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is approved for the treatment of advanced non-small-cell lung cancer (NSCLC) with mutations of EGFR that are sensitive to gefitinib [1, 2]. The use of herbal medicines in combination with antitumour drugs has developed considerable interest [7, 8] It plays a critical role in improving the quality of life of chemotherapy patients with malignant tumours such as lung cancer, colon cancer, and gastric cancer [9, 10]. 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. E results showed that a single intragastrically administered dose of Si Jun Zi Tang increased the pharmacokinetic parameters of gefitinib (Cmax, 3156.13 μg/L; A UC, 46281.5 μg/L/h) by 3 folds in rats compared with the administration of gefitinib alone (Cmax, 1352.07 μg/L; AUC, 11823.7 μg/L/h). Long-term administration of gefitinib in combination with Si Jun Zi Tang would improve the efficacy of gefitinib
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