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 C 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.