A Study on the Effect of Pioglitazone on Pharmacokinetic and Antidepressant Activity of Fluoxetine

Abstract

It is often observed that diabetic patients are more often suffers from depressive disorders.   Depression and diabetes are managed clinically by administering number of drugs for long duration. Hence, polypharmacy are of wide concern in drug-drug interactions which are important cause of adverse drug reactions. The present work studied the possible pharmacokinetic drug interaction between pioglitazone and fluoxetine in healthy albino rats following single and multiple dosage treatment. The effect of pioglitazone on antidepressant activity was studied using three animal models. The serum concentration of fluoxetine was estimated by HPLC and antidepressant activity was studied using despair swim test, tail suspension test and compulsive gnawing test. The concentration of serum fluoxetine was significantly increased after the pioglitazone treatment for 7 days. Maximum concentration was obtained at 4^th hour after administration of pioglitazone. The pharmacokinetic parameters like AUC, AUMC, t_1/2 and Cmax of fluoxetine showed significant changes after pioglitazone treatment for one week in healthy albino rabbits. One week treatment of pioglitazone significantly decreases in immobility time of fluoxetine by despair swim and tail suspension test in rats and mice respectively. The results showed that the interaction between fluoxetine and Pioglitazone may be due to similar metabolic pathway and strong protein binding.