Chronomodulated Nifedipine Supports Concurrent Glimepiride Administration with Subsequent Amelioration of Retinopathy and Peripheral Neuropathy in Diabetic Rats

This study investigated effect of chronomodulated nifedipine on two microvascular complications in glimepiride-treated diabetic rats for 21 days. Groups 1 and 2 were non-diabetic and diabetic controls respectively, receiving 1 ml/kg PEG+H2O. Groups 3-5 were diabetic, receiving 10 mg/kg glimepiride at 2000 hrs. In addition, groups 4 and 5 received nifedipine, 20 mg/kg at 2000 hrs and 0800 hrs respectively. Peripheral neuropathy was evaluated weekly using the paw pressure and tail immersion tests, while retinopathy was evaluated by determining levels of some serum ocular markers, and histological assessment of retina. Treatment with glimepiride alone at 2000 hrs, produced no significant effect on the complications. Treatment with glimepiride and nifedipine at 2000 hrs exacerbated the complications. Conversely, treatment with glimepiride at 2000 hrs and nifedipine at 0800 hrs significantly (P<0.05) ameliorated both complications. These findings suggest that with chronotherapy, both drugs may be used together for the purpose of ameliorating retinopathy and peripheral neuropathy.