| Abstract: | Paclitaxel is one of the cancer drugs commonly used in breast cancer treatment. It is metabolized by the CYP-450 (CYP-450) enzymes. Due to lack of specificity it contains severe side effects. Herbal medicines can be used in managing chemotherapy side effects. They are usually used before, during, and after chemotherapy. Xiang-Sha-Liu-Jun-Zi Tang (XSLJZT) is one of the herbal formula used in managing chemotherapy side effects. It is derived from SJZT and its related decoctions. Its individual herbs contain phytochemicals that can interaction with CYP-450 enzymes and P-gp transporters. In this study the pharmacokinetic influence of XSLJZT on paclitaxel was evaluated. Sprague Dawley rats were pre-administered with XSLJZT for 2 hours or 3, 5, and 7 days before paclitaxel administration. The influence on CYP3A1/2 and CYP3A enzymes expressions was evaluated using rat liver tissues and HepG2 cells respectively. The human liver microsomes were used to determine the influence on enzyme activity. Paclitaxel levels were monitored using the developed LC-MS/MS system. XSLJZT increased the area under the concentration versus time curve (AUC) for paclitaxel by 2-, 3- and 4-fold after 3, 5, and 7 days pre-treatment, respectively. In contrast, no significant change in the AUC was observed in the group pretreated 2 hours prior paclitaxel administration. It also inhibited the expression of CYP3A1/2 and CYP3A4 enzymes. Its related decoctions and individual herbs also inhibited CYP3A4 enzymes. The enzyme activity was inhibited by a competitive reversible mechanism. In conclusion, XSLJZT can potentially interact with paclitaxel and chemotherapeutics metabolized by similar mechanisms. Its related decoctions and individual herbs can potentially cause a similar effect. |
