Diurnal variation in nifedipine PK supports concurrent coadministration with glimepiride in diabetic rats

[Speaker] Temidayo O Olurishe:1
[Co-author] Michael Oraebosi:1, Lydia Ayanwuyi:1
1:Department of Pharmacology and Therapeutics, Ahmadu Bello University Zaria, Nigeria

This study investigated the effect of chronomodulated nifedipine on glycaemic control and nephropathy in glimepiride treated diabetic rats. Groups 1 and 2 were non-diabetic and diabetic controls respectively, receiving PEG+H2O 1 ml/kg. Groups 3-5, all diabetic, received glimepiride 10 mg/kg at 2000 hrs. Groups 4 and 5 received nifedipine 20 mg/kg at 2000 hrs and 0800 hrs respectively in addition. Treatments were oral for 21 days with fasting and random blood glucose determined intermittently. Nephropathy was evaluated by determining renal serum biomarkers, kidney weights and renal histological assessment. Glimepiride alone at 2000 hrs significantly (P<0.01) reduced blood glucose in successive weeks compared to initial values, without alleviation of microvascular complications. Concurrent administration of glimepiride-nifedipine treatment at 2000 hrs impaired glycaemic control and exacerbated microvascular complications. However, treatment with glimepiride at 2000 hrs and nifedipine at 0800 hrs significantly (P<0.01) improved glycaemic control. Treatment with glimepiride alone at 2000 hrs, and concurrent administration of glimepiride and nifedipine at 2000 hrs exhibited renal data similar to diabetic control. However, treatment with glimepiride at 2000 hrs and nifedipine at 0800 hrs revealed significantly (P<0.05) higher serum protein and albumin and significantly (P<0.05) lower serum urea with non-significantly lower serum creatinine and uric acid levels when compared to the diabetic control group. The relative kidney weight was also significantly (P<0.05) lower in this group than the diabetic controls while histological features were similar to the non-diabetic controls. This study suggest that nifedipine and glimepiride may be successfully used with full therapeutic benefit of both.

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