The mechanism of drug interactions of a selected antiarrhythmic drug with metformin, in different animal models

ABSTRACT This study was carried out to understand the influence of a selected antiarrhythmic drug on the pharmacodynamics and pharmacokinetics of an antidiabetic drug in animal models. Pharmacodynamic and pharmacokinetic responses were determined by measurements of blood glucose and serum insulin and serum metformin to drug interactions between disopyramide and metformin. Single dose and multi dose studies showed that the maximum blood glucose reductions in normal and diabetic rats were at the 6th hour, and in rabbits at the 3rd hour. Glucose-insulin homeostasis was evaluated to assess the safety and effectiveness of the combination. There was a marginal increase in the pharmacokinetic parameters of metformin with multiple dose treatments of disopyramide but no significant changes in kinetic parameters between single and multiple dose studies, compared to metformine alone. There may be a possibility of disopyramide and metformin interaction at the excretion stage, or an additive pharmacodynamic action. This study validates the drug interaction in two dissimilar species, which indicates more probability of its occurrence in humans.