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.
Keywords: Diabetes; Disopyramide; Mexiletine; Pharmacodynamics; Thiazolidinediones.