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

Abstract

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].