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

Abstract

Objective

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.

Method

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 MRT and T of imatinib in the experimental group differed significantly from the control group after a single dose (P < 0.05, 95% CI). T and tz of imatinib and AUC and T 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 single-dose administration, but nifedipine did not significantly impact imatinib metabolism after multiple-dose administration.

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2024-12-19
2025-01-22

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The Effect of Nifedipine on the Pharmacokinetics of Imatinib and its Metabolism N-desmethyl Imatinib in Rats
Bentham Science Publishers ; https://doi.org/10.2174/0115734129351390241217051815
/content/journals/cpa/10.2174/0115734129351390241217051815
/content/journals/cpa/10.2174/0115734129351390241217051815
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  • Article Type:     Research Article
Keywords: drug-drug interaction ; pharmacokinetics ; Nifedipine ; n-desmethyl imatinib ; imatinib ; CYP3A4

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