Prediction of Drug–Drug Interaction between Tacrolimus and Principal Ingredients of Wuzhi Capsule in Chinese Healthy Volunteers Using Physiologically‐Based Pharmacokinetic Modelling

• DOI: 10.1111/bcpt.12914
• Publication Date: 2017-09-25T11:32:41Z
• Authors: Hongyan Zhang; Fengjiao Bu; Lei Li; Zheng Jiao; Guo Ma; Weimin Cai; Xiaomei Zhuang; Hai‐Shu Lin; Jae‐Gook Shin; Xiaoqiang Xiang
• Keywords: Capsule

Schisantherin A and schisandrin A, the most abundant active ingredients of Wuzhi capsule, are known to inhibit tacrolimus metabolism by inhibiting CYP3A4/5. We aimed predict contribution schisantherin drug-drug interaction (DDI) between capsule using physiologically-based pharmacokinetic (PBPK) modelling. Firstly, inhibition mechanism on CYP3A4/5 was investigated. Thereafter, PBPK models were established. Finally, pharmacokinetics evaluated after combined use with or A. The blood area under curve (AUC) increased 1.77- 2.61-fold a single dose multiple doses respectively. Meanwhile, inhibited smaller extent. Also, it showed that mechanism-based (MBI) played more important role in DDI than reversible long-term administration, while comparable MBI single-dose administration. In conclusion, we utilized modelling quantify capsule. This may provide insights for rational this drug combination.