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

TL;DR

This study tested how two substances, montmorillonite powder and loperamide, affect the absorption of a drug called pyrotinib in healthy volunteers.

Contribution

The study provides new insights into how co-administered drugs or substances can significantly alter the pharmacokinetics of pyrotinib.

Findings

Montmorillonite powder reduced pyrotinib's maximum concentration and systemic exposure by up to 32.4%.

Loperamide slightly increased pyrotinib's systemic exposure by about 19%.

Montmorillonite powder should not be co-administered with pyrotinib due to significant absorption reduction.

Abstract

To investigate the potential pharmacokinetic interactions of montmorillonite powder or loperamide on pyrotinib.

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.

In Group A, the combination treatment with montmorillonite powder resulted in a decrease in Cmax, AUC0-t, and AUC0-
∞

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 AUC0-t and AUC0-
∞

by approximately 18% and 19%, respectively, while decreasing CL/F and prolonging the t1/2.

Even when montmorillonite powder was administered 2 h after pyrotinib dosing, it still reduced systemic exposure of pyrotinib by 32.4% in AUC0-
∞
. In contrast, loperamide increased pyrotinib exposure by 19% in AUC0-
∞

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.

[ClinicalTrials.gov], identifier [NCT05252546].

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