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