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Anuj Gautam*, N.C.Nagalakshmi, Chandra Prakash Acharya, Manoj Kandel, Amit Shrestha, Manoj Lamichhane.


Depression and hypertension are managed clinically by administering Number of drugs for longer duration. The studies have documented three- fold higher frequency of major depression in patients treated for hypertension extant. These two disorders are long-term disorders, treated with different drugs and there is a chance that the interaction between these drugs may appear which affects the management of single disorder or both disorders. We had studied the effect of losartan treatment on pharmacokinetic parameters and antidepressant activity of fluoxetine. The metabolic pathway for the concerned two drugs losartan and fluoxetine are by the same enzyme, CYP2C9. Healthy male albino rabbits were used to study the effect of losartan on pharmacokinetic parameters of fluoxetine followed by antidepressant activity to confirm the results. The concentration of fluoxetine in serum was estimated by HPLC and antidepressant activity was studied using despair swim test and serotonin syndrome in healthy albino rats. The serum concentration of fluoxetine was found significantly increased after losartan treatment for 7 days. The pharmacokinetic parameters like AUC, AUMC, Tmax, Cmax, t1/2 and MRT of fluoxetine showed changes after losartan treatment for 7 days in healthy albino rabbits. Losartan treatment for one week exhibited significantly decreased in immobility time of fluoxetine tested by despair swim test and the severity of forepaw treading was significantly increased when tested in healthy rats. The results revealed that the drug-drug interaction between fluoxetine and losartan could be due to strong protein binding property of both drugs and due to enzyme inhibition by CYP2C9.

Keywords: Fluoxetine; Losartan; Depression; Hypertension, pharmacokinetics and despair swim test.

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