Influence of atorvastatin on the pharmacodynamic and pharmacokinetic activity of repaglinide in rats and rabbits.
Dyslipidemia is common in patients with type 2 diabetes. Statins are used as the first choice in treatment of diabetic dyslipidemia. Atorvastatin represents a first-line treatment option, alongside other hydroxyl methylglutaryl coenzyme A reductase inhibitors. Repaglinide is a short-acting, oral, insulin secretagogue that is used in the treatment of type 2 diabetes mellitus. Both the category of drugs undergo extensive metabolism with cytochrome enzyme system. This may lead to drug-drug interaction problems with altered repaglinide activity which is cautious. Repaglinide/atorvastatin/atorvastatin + repaglinide were administered orally to normal, diabetic rats, and to normal rabbits. Blood samples were collected at different time intervals and were analyzed for blood glucose by GOD-POD method using commercial glucose kits and repaglinide estimation in plasma by HPLC method. Diabetes was induced by alloxan 100 mg/kg body weight administered by I.P route. In the presence of atorvastatin, repaglinide activity was increased and maintained for longer period in diabetic rats compared with repaglinide matching control. The present study concludes co-administration of atorvastatin was found to improve repaglinide responses significantly in diabetic rats and improved glucose metabolism of atorvastatin played an important role and increased repaglinide levels by competitive CYP 3A4 enzyme inhibition by atorvastatin could be added advantage for anti hyperglycemic activity.
Gurram Balanarasaiah Institute of Pharmacy, Ghatkesar, R.R. Dist, Hyderabad, Andhra Pradesh, India. manikanta.chandra@gmail.com
Makula Chandra
MC
Sekhar
P Jaya Chandra
PJ
Reddy
D000818:Animals; D000069059:Atorvastatin; D001786:Blood Glucose / Q000187:drug effects*; D002219:Carbamates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004347:Drug Interactions; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats
D001786:Blood Glucose; D002219:Carbamates; D065607:Cytochrome P-450 Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D010880:Piperidines; D011758:Pyrroles; C072379:repaglinide; D000069059:Atorvastatin; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A