Abstract
This study investigated the effect of imatinib on the pharmacokinetics and pharmacodynamics of glibenclamide in alloxan-induced diabetic rats, as both drugs were reported to be CYP2C9 substrates. The control and test groups (n = 5) were treated for seven consecutive days with vehicle and imatinib (50 mg/kg), respectively. On day seven, 1 h after the last dose of imatinib, both groups were administered glibenclamide (10 mg/kg). Blood samples were collected in heparinized tubes at different time points (1, 2, 4, 8, and 12 h) from the retro-orbital plexus to determine blood glucose and glibenclamide plasma concentrations by glucose test strips and a UPLC-MS/MS analytical method, respectively. Imatinib increased the glibenclamide peak plasma concentration (C-max) and the area under the plasma concentration-time curve (AUC(0-t)) by 2.75 and 2.29 fold, respectively (P < 0.05). Blood glucose level was significantly reduced. Imatinib significantly increased glibenclamide plasma concentration and the glibenclamide hypoglycemic effect. Inhibition of CYP2C-mediated glubenclamide metabolism may be involved.