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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Research Article

Pharmacokinetic Interaction between Imatinib and Tacrolimus in Rats

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

Volume 25, Issue 8, 2024

Published on: 23 December, 2024

Page: [613 - 621] Pages: 9

DOI: 10.2174/0113892002319356241210073350

Price: $65

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Abstract

Objective: Tacrolimus, a calcineurin inhibitor (CNI), is the first-line treatment for chronic myeloid leukemia (CML) and advanced gastrointestinal stromal tumors (GIST). Imatinib and tacrolimus are both substrates of the hepatic enzymes CYP3A4/5 and efflux transporter P-gp, so drug-drug interactions may occur during their co-administration treatment. Therefore, this study aimed to evaluate the pharmacokinetic interaction between imatinib and tacrolimus in rats.

Methods: Rats were divided into groups I (30 mg/kg imatinib administered for 14 days), II (1.89 mg/kg tacrolimus and 30 mg/kg imatinib administered for 14 days), III (30mg/kg imatinib and 0.63mg/kg tacrolimus administered for 14 days), IV (1.89mg/kg tacrolimus for 14 days), and V (10mg/kg imatinib and 1.89mg/kg tacrolimus for 14 days). Blood samples were determined for whole blood of tacrolimus, plasma of imatinib, and Ndesmethyl imatinib concentrations using ultra-performance liquid chromatography-mass spectrometry.

Results: After 1 day of a single dose, tacrolimus had no significant effect on the pharmacokinetics of imatinib and N-desmethyl imatinib; imatinib significantly increased the AUC and Cmax of tacrolimus (P < 0.05). After 14 days of multiple doses, tacrolimus significantly reduced the AUC and Cmax of imatinib and N-desmethyl imatinib (P < 0.05). Further, imatinib significantly increased AUC0-24 and AUC0-∞ of tacrolimus (P < 0.05).

Conclusion: Imatinib increased tacrolimus blood concentrations after single and multiple administrations. Tacrolimus did not significantly affect the pharmacokinetics of imatinib after a single dose; however, tacrolimus might impact the absorption and metabolism of imatinib after multiple doses. The results showed that when imatinib and tacrolimus were co-administered, attention should be paid to the presence of drug-drug interactions.

Keywords: Tacrolimus, imatinib, N-desmethyl imatinib, pharmacokinetic, drug-drug interaction, hepatic enzymes.

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