Abstract
Background: Polypharmacy is of wide concern in drug interaction. It is the leading cause of adverse drug reaction, and consequently, increasing the possibility of hospitalization and escalating the cost of care. The incidence of coexisting depression and hyperlipidemia in patients is generally managed by providing numerous drugs for a longer period of time.

Aims and Objectives: This study was conducted to observe the effect of atorvastatin on pharmacokinetic parameters of fluoxetine in healthy albino rabbits and to find possible interactions of atorvastatin on the antidepressant activity of fluoxetine using animal screening test.

Materials and Methods: Two drugs: Fluoxetine and atorvastatin used concurrently were selected. Healthy male albino rabbits were used to determine the effect of atorvastatin on fluoxetine addressing its pharmacokinetic parameters, whereas rats and mice were used to assess the antidepressant activity of fluoxetine. Two animal models were used to determine its antidepressant activity. Forced swim test (FST) and tail suspension test (TST) were employed in exploring antidepressant activity. High-performance liquid chromatography was used to estimate fluoxetine concentration.

Results: The concentration of serum fluoxetine showed slight increment after the atorvastatin treatment for 7 days at 2nd, 4th, 8th, 16th, and 24th h. The pharmacokinetic parameters: Area under the curve, area under first-order moment curve, t1/2, and Cmax of fluoxetine varied after atorvastatin treatment for 1 week in healthy albino rabbits. ‘’Furthermore, atorvastatin treatment for a week revealed a reduction in immobility time in rats and mice as shown by the FST and TST respectively.

Conclusion: The results revealed the possibility of drug-drug interaction between fluoxetine and atorvastatin.

Key words: Depression; Fluoxetine; Atorvastatin; Drug-drug Interaction; Forced Swim Test, Tail Suspension Test