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Influence of atorvastatin on the pharmacodynamic and pharmacokinetic activity of repaglinide in rats and rabbits

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Abstract

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.

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Abbreviations

HMG-CoA:

Hydroxyl methylglutaryl coenzyme A

ATP:

Adenosine tri phosphate

GOD/POD method:

Glucose oxidase and peroxidase method

SEM:

Standard error mean

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Acknowledgments

We are thankful to Shekar Sunkoju (Biostatistian, Max Neeman International, New Delhi-110020) for assistance in statistical analysis.

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Authors and Affiliations

  1. Gurram Balanarasaiah Institute of Pharmacy, Ghatkesar, R.R. Dist, Hyderabad, Andhra Pradesh, India

    Makula Chandra Sekhar

  2. Jawaharlal Nehru Technological University, Hyderabad, Andhra Pradesh, India

    Makula Chandra Sekhar

  3. Krishna Teja Pharmacy College, Tirupathi, Andhra Pradesh, India

    P. Jaya Chandra Reddy

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  1. Makula Chandra Sekhar
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  2. P. Jaya Chandra Reddy
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Correspondence to Makula Chandra Sekhar.

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Sekhar, M.C., Reddy, P.J.C. Influence of atorvastatin on the pharmacodynamic and pharmacokinetic activity of repaglinide in rats and rabbits. Mol Cell Biochem 364, 159–164 (2012). https://doi.org/10.1007/s11010-011-1214-6

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  • DOI: https://doi.org/10.1007/s11010-011-1214-6

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