Title:The Effect of Nifedipine on the Pharmacokinetics of Imatinib and its Metabolism N-desmethyl Imatinib in Rats
Volume: 20
Issue: 9
Author(s): Naling Fan, Liying Du, Teng Guo, Mingfeng Liu and Xinran Chen*
Affiliation:
- Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Hebei Key Laboratory of Clinical
Pharmacy, Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, Hebei Province, P.R. China
Keywords:
Nifedipine, imatinib, n-desmethyl imatinib, drug-drug interaction, pharmacokinetics, CYP3A4.
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.