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2000
Volume 25, Issue 8
  • ISSN: 1389-2002
  • E-ISSN: 1875-5453

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 N-desmethyl 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 C of tacrolimus (P < 0.05). After 14 days of multiple doses, tacrolimus significantly reduced the AUC and C of imatinib and N-desmethyl imatinib (P < 0.05). Further, imatinib significantly increased AUC and AUC 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.

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2024-12-23
2025-10-30

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Pharmacokinetic Interaction between Imatinib and Tacrolimus in Rats
Current Drug Metabolism 25, 613 (2024); https://doi.org/10.2174/0113892002319356241210073350
/content/journals/cdm/10.2174/0113892002319356241210073350
/content/journals/cdm/10.2174/0113892002319356241210073350
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  • Article Type:     Research Article
Keyword(s): drug-drug interaction; hepatic enzymes; imatinib; N-desmethyl imatinib; pharmacokinetic; Tacrolimus

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