ABSTRACT
Glibenclamide is extensively metabolized in the liver through oxidative pathways involving the cytochrome P450 system. Fluvoxamine, a potent inhibitor of cytochrome P450 [CYP] isoenzymes may be coadministered with glibenclamide. The aim of this study was to investigate whether or not fluvoxamine influences the pharmacokinetics of glibenclamide after multiple oral doses of both drugs in rats. Eighteen rats were divided into 3 groups for blood sampling. All rats received oral dose of 2.5 mg/kg for 7 days. Blood samples were collected up to 24 h after the initial dose, and on day 7 for glibenclamide. On day 8, a daily oral dose of fluvoxamine [50 mg/kg] was added and the administration of the two drugs were continued for 7 more days. On day 14, blood samples were also collected for the determination of both glibenclamide and fluvoxamine. Results indicated that following the single dose administration, glibenclamide C [max], was 415 +/- 169ng/ml, T[max], was 3.7 +/- 1.4h, t[1/2] was about 12 h and apparent clearance [C1/F] was 629 ml h[-1]kg[-1]. However, multiple dose administration of glibenclamide increased the AUC by 30% compared to the single dose. On the other hand, fluvoxamine coadministration was associated with a 16% increase in ACU. There was no significant change [p>0.05] in either C[max], or T[max]. A twenty% reduction in C1/F of glibenclamide was observed, however the difference was not significant. Therefore, the administration of fluvoxamine did not significantly alter glibenc1amide pharmacokinetic parameters. Further studies in diabetic rats or human should be performed, for a long period of time, to demonstrate if such interaction between fluvoxamine and glibenclamide is of pharmacokinetic and /or pharmacodynamic significance