Effects of Resveratrol on pharmacokinetics and pharmacodynamics of Pioglitazone in Diabetic rats

Abstract

Introduction: Diabetes is a group of metabolic disorders characterized by a chronic hyperglycaemic condition resulting from insufficient action of insulin. CYP inhibiting drugs increase the concentration of the drugs that are substrates for the specific CYP isoforms and thus enhance the pharmacological and toxicological effects of the substrate drugs. Pioglitazone is a CYP3A4 substrate and resveratrol is a strong inhibitor. Hence, there is a chance of influence on the pharmacokinetics and pharmacodynamics of Pioglitazone. Materials & Methods: The study was performed on male wistar rats, divided into five groups. Diabetes was induced by administration of Streptozotocin 45mg/kg in 0.1M citrate buffer. Diabetic rats were treated with resveratrol before administration of pioglitazone. Blood samples were collected from orbital puncture at various time intervals and analysed for blood glucose and pharmacokinetics of pioglitazone by HPLC. Results: serum concentration (mcg/ml) of pioglitazone increased in diabetic rats supplemented with resveratrol. Conclusion: The results of increased pioglitazone levels as a result of its metabolic inhibition under resveratrol exposure suggests an interaction which may be due to decreased metabolism of pioglitazone as a result of CYP3A4 and CYP2C8 inhibition.

Keywords

• type 2 diabetes
• pioglitazone
• resveratrol
• wistar rats
• pharmacokinetics