Gurram Balanarasaiah Institute of Pharmacy, Ghatkesar, R.R. Dist, Hyderabad, Andhra Pradesh, India.
Mol Cell Biochem. 2012 May;364(1-2):159-64. doi: 10.1007/s11010-011-1214-6. Epub 2012 Jan 7.
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.
血脂异常在 2 型糖尿病患者中很常见。他汀类药物被用作治疗糖尿病血脂异常的首选药物。阿托伐他汀是羟甲基戊二酰辅酶 A 还原酶抑制剂的一线治疗选择。瑞格列奈是一种短效、口服、胰岛素促分泌剂，用于治疗 2 型糖尿病。这两类药物都经过细胞色素酶系统的广泛代谢。这可能会导致与瑞格列奈活性改变相关的药物相互作用问题，需要谨慎。将瑞格列奈/阿托伐他汀/阿托伐他汀+瑞格列奈分别口服给予正常、糖尿病大鼠和正常兔。在不同的时间间隔采集血样，并通过 GOD-POD 法使用商业葡萄糖试剂盒分析血糖，通过 HPLC 法分析血浆中的瑞格列奈。糖尿病通过腹腔注射 100mg/kg 体重的链脲佐菌素诱导。在阿托伐他汀存在的情况下，与瑞格列奈匹配对照相比，糖尿病大鼠中瑞格列奈的活性增加并维持更长时间。本研究得出结论，阿托伐他汀的联合用药在糖尿病大鼠中显著改善了瑞格列奈的反应，阿托伐他汀对葡萄糖代谢的改善起到了重要作用，通过阿托伐他汀竞争性 CYP3A4 酶抑制增加瑞格列奈水平可能是抗高血糖活性的优势。
