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Evaluation of the pharmacokinetic interactions of montmorillonite powder or loperamide on pyrotinib in healthy volunteers

Affiliation
Department of Clinical Pharmacology ,Jiangsu Hengrui Pharmaceuticals Co., Ltd. ,Shanghai ,China
Wang, Yike;
Affiliation
Phase I Clinical Trial Center ,Xiangya Hospital ,Central South University ,Changsha ,China
Li, Dai;
Affiliation
Department of Clinical Pharmacology ,Jiangsu Hengrui Pharmaceuticals Co., Ltd. ,Shanghai ,China
Zhang, Tong;
Affiliation
Phase I Clinical Trial Center ,Xiangya Hospital ,Central South University ,Changsha ,China
Xu, Sumei;
Affiliation
Phase I Clinical Trial Center ,Xiangya Hospital ,Central South University ,Changsha ,China
Zhang, Yanxin;
Affiliation
Department of Clinical Pharmacology ,Jiangsu Hengrui Pharmaceuticals Co., Ltd. ,Shanghai ,China
Zhao, Kaijing;
Affiliation
Department of Clinical Pharmacology ,Jiangsu Hengrui Pharmaceuticals Co., Ltd. ,Shanghai ,China
Li, Shaorong;
Affiliation
Department of Clinical Pharmacology ,Jiangsu Hengrui Pharmaceuticals Co., Ltd. ,Shanghai ,China
Shen, Kai;
Affiliation
Phase I Clinical Trial Center ,Xiangya Hospital ,Central South University ,Changsha ,China
Li, Xiaomin;
Affiliation
Phase I Clinical Trial Center ,Xiangya Hospital ,Central South University ,Changsha ,China
Xu, Pingsheng

Aims To investigate the potential pharmacokinetic interactions of montmorillonite powder or loperamide on pyrotinib. Methods This study was a single-center, open-label, single-dose, fixed-sequence clinical trial conducted with healthy volunteers. The participants were divided into two groups (A and B), each consisting of 18 subjects. Both groups received a single oral dose of 400 mg of pyrotinib on day 1. On day 9, Group A received a single dose of 400 mg of pyrotinib followed by 3 g of montmorillonite powder 2 h later, while Group B received a single dose of pyrotinib and 4 mg of loperamide after breakfast on day 9, followed by single oral doses of 2 mg of loperamide at 2 and 4 h post-administration. Blood samples were collected to determine pyrotinib blood concentrations. Results In Group A, the combination treatment with montmorillonite powder resulted in a decrease in C max , AUC 0-t , and AUC 0- ∞ by 26.7%, 33.1%, and 32.4%, respectively, compared to pyrotinib alone. In Group B, the combination treatment with loperamide had minimal impact on pyrotinib’s absorption rate but slightly increased AUC 0-t and AUC 0- ∞ by approximately 18% and 19%, respectively, while decreasing CL/F and prolonging the t 1/2 . Conclusion Even when montmorillonite powder was administered 2 h after pyrotinib dosing, it still reduced systemic exposure of pyrotinib by 32.4% in AUC 0- ∞ . In contrast, loperamide increased pyrotinib exposure by 19% in AUC 0- ∞ when used together. Based on these findings, loperamide is recommended for symptom control, while montmorillonite powder should not be co-administered with pyrotinib or any drug requiring optimal absorption. Clinical trial registration [ ClinicalTrials.gov ], identifier [NCT05252546].

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License Holder: Copyright © 2025 Wang, Li, Zhang, Xu, Zhang, Zhao, Li, Shen, Li and Xu.

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