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

Abstract EN

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 Cmax of paclitaxel in plasma were significantly reduced by approximately 1.5-fold, compared to paclitaxel alone.

Additionally, JWXYS decreased the AUC and Cmax 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.