EVALUATION OF STEADY STATE PHARMACOKINETICS AND SAFETY OF DULOXETINE IN INDIAN MAJOR DEPRESSIVE PATIENTS AFTER MULTIPLE DOSING IN HOSPITAL SET UP

Duloxetine belongs to drug class of anti-depressants. Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor. An earlier open label, randomised, comparative, two arms, multicentric clinical trial was conducted to evaluate the safety and efficacy of duloxetine in comparison to venlafaxine in the treatment of major depression in Indian patients. Pharmacokinetic parameters were evaluated in some of the patients randomized to duloxetine by an open label extension of previously conducted phase trial as mentioned earlier. The doses of Duloxetine 20mg, 40mg and 60mg were administered to the patients who continued duloxetine after completion of the earlier mentioned clinical trial. Plasma concentrations were measured on days 15, days 29 and on days 43 after administration of duloxetine to the major depressive patients as a same dose they have been prescribed after completion of previous clinical trial. Plasma concentrations of duloxetine were quantified in order to evaluate the essential pharmacokinetic parameters The mean Cmax , Cmin , Cavg , AUCτ , Tmax, t 1/2, , , % PTF for Duloxetine 40mg and 60mg were found to be [93.640 ng/ml,49.860 ng/ml, 68.359 ng/ml, 820.305 hr.ng/ml, 5.000 hrs, 10.189 hrs, 54.406];[158.020 ng/ml, 86.100 ng/ml, 116.971 ng/ml, 1403.655 hr.ng/ml, 5.4000 hrs, 11.869 hrs, 52.233] respectively. Duloxetine in the dose range of 20mg to 60mg was very well tolerated during the pharmacokinetic study.