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

Ying Li; Xiaowei Zhou; Ming Niu; Mingyu Zhang; Qiong Gu; Wei Chen; Bin Dong; Yuanyuan Zhang; Ruisheng Li; Chunyu Li; Guohui Li

doi:10.1155/2021/6655449

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

Evid Based Complement Alternat Med. 2021 Jul 26:2021:6655449. doi: 10.1155/2021/6655449. eCollection 2021.

Authors

Ying Li¹, Xiaowei Zhou¹, Ming Niu², Mingyu Zhang¹, Qiong Gu¹, Wei Chen¹, Bin Dong¹, Yuanyuan Zhang¹, Ruisheng Li³, Chunyu Li¹, Guohui Li¹

Affiliations

¹ Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Integrative Medical Center, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.
³ Research Center for Clinical and Translational Medicine, The Fifth Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.

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.