INFLUENCE OF VERAPAMIL ON PHARMACOKINETICS OF PIOGLITAZONE IN NORMAL AND DIABETIC RATS

摘要

The study was undertaken to find out the pharmacokinetic drug interaction of verapamil on pioglitazone in normal and alloxan induced diabetic rats following single and multiple dose treatment. Human oral therapeutic doses of pioglitazone and verapamil were extrapolated to rats based on their body surface area. The serum pioglitazone concentrations were estimated by a sensitive reverse phase – high performance liquid chromatography (RP-HPLC) method. In single and multiple dose study, verapamil significantly increased the pioglitazone exposure (AUC, C_max) and decreased its elimination by prolongation of t_1/2 and mean residence time (MRT) with a relative decrease in clearance (CL). The effect is more significant in diabetic rats. In the present study a pharmacokinetic interaction between verapamil and pioglitazone was observed. The possible interaction may involve both P-glycoprotein and CYP enzymes. Investigating this type of interactions pre-clinically is helpful to avoid drug-drug interactions in actual clinical situation.