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

Peptic ulcer and Depression are managed by co-administering number of drugs for long duration. Hence, drug-drug interactions which are important cause of antagonistic drug reaction and may lead to amplified risk of hospitalization and amplified care cost. The study was piloted to find the impact of pantoprazole which is generally used for primary peptic ulcer disease in humans on the pharmacokinetic and antidepressant activity of fluoxetine. The influence of pantoprazole on pharmacokinetic parameters of fluoxetine was studied in healthy male albino rabbits. The effect of pantoprazole on antidepressant activity was studied using four animal models. The serum concentration of fluoxetine was estimated by HPLC. And the antidepressant activity was studied using despair swim test, compulsive gnawing test, serotonin syndrome and tail suspension test. After treating with pantoprazole for 7 days the concentration of serum fluoxetine was significantly decreased at 2nd, 4th, 8th, 16th and 24th hour. Pantoprazole treatment for one week exhibited significantly changes in the pharmacokinetic parameters like AUC, AUMC, t1/2 and Cmax of fluoxetine in healthy albino rabbits. The immobility time significantly decreases after pantoprazole treatment for one week by despair swim and tail suspension test in rats and mice respectively. Compulsive gnawing test and serotonin syndrome also shows decrease in the effect after pantoprazole treatment. When both drugs are co-administered together dose of fluoxetine should be increased. Key words: Depression; Fluoxetine; Pantoprazole; Drug-drug interaction; Tail Suspension test; Despair Swim Test.