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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

The Effect of Nifedipine on the Pharmacokinetics of Imatinib and its Metabolism N-desmethyl Imatinib in Rats

Author(s): Naling Fan, Liying Du, Teng Guo, Mingfeng Liu and Xinran Chen*

Volume 20, Issue 9, 2024

Published on: 19 December, 2024

Page: [1092 - 1101] Pages: 10

DOI: 10.2174/0115734129351390241217051815

Price: $65

Abstract

Objectives: Imatinib is a first-line medicine for chronic myeloid leukemia (CML) and gastrointestinal mesenchymal stromal tumors (GIST). Co-administration of nifedipine may lead to drug-drug interactions that affect the clinical efficacy of imatinib. Imatinib and nifedipine are substrates for the cytochrome enzyme CYP3A4. This study aimed to research the pharmacokinetic effect of nifedipine on imatinib and its metabolism N-desmethyl imatinib in rats.

Methods: Twenty healthy SD rats were randomly divided into two groups. The control group was administered imatinib by gavage for 14 days, and the experimental group was co-administered imatinib and nifedipine by gavage for 14 days. The plasma concentrations of imatinib and N-desmethyl imatinib in rats were determined by ultra-performance liquid chromatography-mass spectrometry.

Results: The MRT0-∞ and Tmax of imatinib in the experimental group differed significantly from the control group after a single dose (P < 0.05, 95% CI). Tmax and t1/2z of imatinib and AUC0-∞ and Tmax of N-desmethyl imatinib were also obviously different between the two groups after multiple doses (P < 0.05, 95% CI).

Conclusion: The study showed that nifedipine might inhibit the imatinib metabolism after singledose administration, but nifedipine did not significantly impact imatinib metabolism after multiple- dose administration.

Keywords: Nifedipine, imatinib, n-desmethyl imatinib, drug-drug interaction, pharmacokinetics, CYP3A4.

Graphical Abstract
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