INFLUENCE OF VERAPAMIL ON PHARMACOKINETICS OF PIOGLITAZONE IN NORMAL AND DIABETIC RATSAbstract
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, Cmax) and decreased its elimination by prolongation of t1/2 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.
Ravikanth Chintala , Chaitanya Gadiko , Bhikku Angoth and Narsimha Reddy Yellu*
Associate Professor, Pharmacology & Clinical Pharmacology Division, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, India – 506009
11 November, 2012
13 December, 2012
15 February, 2013
01 March, 2013