Gliclazide-Topiramate Interaction Studies in Rats and Rabbits

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A BSTRACT Introduction: There is a chance of drug–drug interactions on glycemic control when two or more drugs are used in the management of diabetes. Topiramate is primarily indicated for neurological disorders but can exhibit additional metabolic actions like weight reduction and improvement in glucose handling. This raises a possibility that topiramate may modify gliclazide’s pharmacodynamic or pharmacokinetic behavior. Aim: The aim of this study was to understand the pharmacodynamic and pharmacokinetic interactions of topiramate on gliclazide action in rodents and nonrodents. Materials and Methods: The study was carried out in normal and alloxan-treated diabetic rats and in normal rabbits. Animals received gliclazide or topiramate alone, or in combination, either as a single dose administration or after repeated dosing. Blood glucose was measured at predefined intervals using glucometer with glucose test strips, and in rabbits, additionally, serum gliclazide levels were measured to assess the influence of topiramate on the absorption and disposition of gliclazide. Results: Topiramate produced a modest glucose-lowering effect on its own; however, the reduction was more pronounced when it was given along with gliclazide. This synergistic enhancement was pronounced after 7 days of topiramate treatment. Diabetic rats were particularly responsive. In rabbits, topiramate caused only small increases in gliclazide exposure, which did not fully account for the marked improvement in glucose control. Conclusions: Co-administration of topiramate strengthened gliclazide’s antihyperglycemic activity, largely through pharmacodynamic influence rather than major alterations in drug kinetics. While the combination appeared well tolerated in the animal models studied, monitoring of blood glucose is advisable when these drugs are co-administered to avoid excessive falls in blood glucose.