Abstract

The present study evaluated whether clarithromycin modifies the glucose-lowering response of gliclazide in experimental animal models. Studies were conducted in normal rats, alloxan-induced diabetic rats, and normal rabbits using a period-wise crossover design that included gliclazide alone, clarithromycin alone, and their combination following either single-dose or multiple-dose clarithromycin pretreatment, with a 10 d washout between periods. Blood glucose levels were measured at predefined time points using the glucose-oxidase-peroxidase method. Gliclazide produced a biphasic hypoglycaemic response in rats, with peak effects observed at 2 h and 8 h, whereas a single peak at approximately 3 h was observed in rabbits. Clarithromycin alone did not produce any consistent effect on blood glucose. In contrast, clarithromycin pretreatment significantly enhanced both the magnitude and duration of gliclazide-induced hypoglycaemia in rats and rabbits, with a more pronounced effect following multiple-dose pretreatment. These findings indicate a clinically relevant interaction, highlighting the importance of careful glucose monitoring when clarithromycin is prescribed in patients receiving gliclazide.