Interactions of Rosiglitazone and Anti-Arrhythmic Drugs in Animal Model

BACKGROUND Diabetes increases the risk of vascular problems by two times compared with a healthy individual, with deposition of fats in blood vessel and this includes cardiovascular disease. The treatment regimens for patients suffering from both diseases generally include prolonged use of anti-diabetic drugs for diabetes and anti-arrhythmic drugs for cardiac arrhythmias. AIM The aim of the study is to compare the influence of Mexiletine and Disopyramide on the pharmacodynamics (PDs) of Rosiglitazone in normal and diabetic rats. MATERIALS AND METHODS The study was conducted in normal rats and diabetic induced rats (with Alloxan monohydrate 100 mg/kg body weight). Albino rats weighing between 160 and 280 g were administered oral doses of Rosiglitazone 0.72 mg/kg, Mexiletine 36 mg/kg, or Disopyramide 18 mg/kg of bodyweight and their combination, with 1 week of washout between treatments. Eighteen rats were divided into three sub-sets with six rats in each sub-set. After 4 days, the blood glucose was estimated to confirm the diabetes. The Analysis of Covariance (ANCOVA) using MedCalc(®) software Version 11.6.1.0 was performed to analyze mean change in blood glucose between treatments with body weight as co-variable and treatment as factor for normal and diabetic rats. RESULTS No statistically significant difference in mean change in blood glucose between Rosiglitazone in comparison with Rosiglitazone + Mexiletine or Rosiglitazone + Disopyramide was observed in normal and diabetic rats (P = 0.606). The maximum mean change in blood glucose for Rosiglitazone and Rosiglitazone + Mexiletine or Rosiglitazone + Disopyramide was observed at 1 h and 8 h in normal and diabetic rats. The post hoc analysis showed baseline correction method has increased the reliability of the results (P < 0.001). CONCLUSION The study concludes that PD activity of Rosiglitazone was not affected by the anti-arrhythmic drugs. This study introduced a new statistical methodology for analyzing the blood glucose endpoint.