Influence of HMG Co-A inhibitor pitavastatin on pharmacodynamics and pharmacokinetics of pioglitazone in rats and rabbits

Venkata Sunil Kumar M., Ramesh A., Padmanabha Reddy Y.


Objective: The study was conducted in rats and rabbits with selected oral doses of Pioglitazone and Pitavastatin their combination to evaluate the safety of Pioglitazone therapy in the presence of Pitavastatin.

Methods: Blood samples were collected from rats/rabbits by retro orbital/marginal ear vein puncture respectively at regular intervals of time. The blood glucose was estimated by GOD/POD method and serum Pioglitazone levels by HPLC method.

Results:  Pitavastatin showed to reduced blood glucose levels alone and with combination of Pioglitazone in both normal rats and diabetic rats. The serum Pioglitazone levels were increased significantly and pharmacokinetic parameters like AUC, Cmax, Ka, Cl and increase in the T1/2 of Pioglitazone were not altered significantly in presence of Pitavastatin.

Conclusion: The combination might be safe with respect to its hypoglycemic effect; so the doses of Pioglitazone and Pitavastatin are advised to safe when co administered in a clinical situation


Pioglitazone, Pitavastatin, Blood Glucose

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Eswar Kumar K, Jyotsna Rani P, Raghu Ram K, Swathi P and Gupta MN. Pharmacodynamic and pharmacokinetic drug interaction of gliclazide and risperidone in animal models. Int J Pharm Pharm Sci, 2012; 4 (2): 659-660.

Inzucchi SE. Management of hyperglycemia in type 2 diabetes: A patient-centered approach. Diabetes Care 2012; 35(6): 1364-1379.

Bharti C, Rahul M, Bairy KL. Statin use and risk of diabetes mellitus. World J Diabetes 2015; 6(2): 352-357.

Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006; 80(6):565-81.

Gillies PS, Dunn, CJ. Pioglitazone. Drugs 2000; 60 (2): 333–45.

Carr A, Samaras K, Chisholm DJ, Cooper DA: Pathogenesis of protease-inhibitorassociated syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance. Lancet 1998; 351:1881–83.

Trinder P. Determination of blood glucose using an oxidaase-peroxidase system with a non carcinogenic Chemogen. J Clin Pathol.1961; 22: 158-161.

Houee C, Gardes M, Pucheault J, Ferradini C. Radical chemistry of alloxan-dialuric acid: role of the superoxide radical, Bull. Eur. Physiopathol. Respir. 1981; 17: 43-48.

Jaakkola T, Laitila J, Neuvonen PJ, Backman JT. Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic clin pharmacol toxicol. 2006; 99(1):44-51.

Schambelan M, Benson CA, Carr A, et al: Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: recommendations of an International AIDS Society-USA Panel. J Acquir Immune Defic Syndr 2002; 33: 257-275.

Flegal, K.M. and Troiano, R.P. Changes in the distribution of body mass index of adults and children in the US population. International Journal of Obesity and Related Metabolic Disorders 2000; 24: 807-818.

Paget, G. E. and Barnes, J. M., Toxicity tests. In Evaluation of Drug Activities: Pharmacometrics (eds Lawrence, D. R. and Bacharach, A. L.), Academic Press, London 1964; 140–161.

Ishihara Y, Ohmori K, Mizukawa M, Hasan AU, Noma T, et al. Beneficial direct adipotropic actions of pitavastatin in vitro and their manifestations in obese mice. Atherosclerosis 2010; 212: 131-138.

Saurabh S, Shalini G, Devendra Kumar, and Rakesh Kumar D. Re-Evaluating Antidiabetic Effect of Pioglitazone in Alloxan Induced Diabetic Animal Model. Research and Reviews: Journal of Pharmacology and Toxicological Studies. 2013; 1(2):52-55.


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