Effects of Jia‐Wei‐Xiao‐Yao‐San on the Peripheral and Lymphatic Pharmacokinetics of Paclitaxel in Rats

Abstract

Paclitaxel is effective against breast cancer. The herbal medicine, Jia-Wei-Xiao-Yao-San (JWXYS), is the most frequent prescription used to relieve the symptoms of breast cancer treatments. The aim of the study was to investigate the herb-drug interaction effects of a herbal medicine on the distribution of paclitaxel to lymph. A validated ultraperformance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was used to determine the paclitaxel levels in rat plasma and lymph after intravenous infusion of paclitaxel alone with or without 7 days of JWXYS pretreatment. The pharmacokinetic results indicate that paclitaxel concentrations in plasma exceeded those in lymph by approximately 3.6-fold. The biodistribution of paclitaxel from plasma to lymph was 39 ± 5%; however, this increased to 45 ± 4% with JWXYS pretreatment. With JWXYS pretreatment, the AUC and C max of paclitaxel in plasma were significantly reduced by approximately 1.5-fold, compared to paclitaxel alone. Additionally, JWXYS decreased the AUC and C max of paclitaxel in lymph. However, the lymph absorption rate of paclitaxel with or without JWXYS pretreatment was not significantly changed (27 ± 3 and 30 ± 2%, resp.). Our findings demonstrate that when paclitaxel is prescribed concurrently with herbal medicine, monitoring of the blood pharmacokinetics of paclitaxel is recommended.

Concurrent administration of anticancer chemotherapy drug and herbal medicine on the perspective of pharmacokinetics

“…Additionally, paclitaxel is approved as a first-line therapy for metastatic breast cancer and has been likely administered with JWXYS in Taiwan; therefore, an investigation of the impact of JWXYS during coadministration with paclitaxel from a pharmacokinetic perspective is valuable for providing information for clinical users. Hou et al studied the herb–drug interactions of JWXYS and paclitaxel in rodent species [ 34 ], and reported that the plasma AUC of paclitaxel in the paclitaxel alone group was approximately 1.5-times higher than that in the group that received oral JWXYS daily for seven days and a single dose of paclitaxel. Furthermore, after pretreatment with JWXYS for seven days, the half-life of paclitaxel increased from 73 min to 111 min, and the clearance increased approximately 1.4-fold compared to paclitaxel alone [ 33 ].…”

“…Furthermore, after pretreatment with JWXYS for seven days, the half-life of paclitaxel increased from 73 min to 111 min, and the clearance increased approximately 1.4-fold compared to paclitaxel alone [ 33 ]. Interestingly, JWXYS rarely affected the lymphatic absorption rate or the lymphatic distribution, but it influenced the metabolic enzymes and intestinal absorption, resulting in an obvious reduction in plasma paclitaxel levels [ 34 ].…”