TDM9 SINGLE-DOSE, RANDOMIZED, CROSS-OVER, BIOAVAILABIUTY PILOT CLINICAL TRIAL OF TORASEMIDE IMMEDIATE RELEASE COMPARED TO A NEW PROLONGED RELEASE FORMULATION OF TORASEMIDE

摘要

Objectives: To evaluate the bioavailability of a new prolonged release formulation of Torasemide (Torasemide-PR) compared to the one of the immediate release formulation of Torasemide (Torasemi-de-IR) available in the market.Setting: Intra-hospital Phase-I Unit.Methods: The bioavailability of two dosages (5 mg and 10 mg) of a new prolonged release formulation of Torasemide was compared to the one of the immediate release formulation of Torasemide in a single-dose, randomized, cross-over, pilot clinical trial. The study included 20 healthy volunteers who were divided in two groups. One group received one administration of 5 mg Torasemide-PR and one administration of 5 mg Torasemide-IR separated by a minimum of 7 days wash-out period. The second group received one administration of 10 mg Torasemide-PR and one administration of 10 mg Torasemide-IR separated by a minimum of 7 days wash-out period. Blood samples were obtained for determination of pharmacokinetic parameters. Urine was collected for total volume, and electrolyte determination. Safety and tolerability were also assessed. Results: The plasmatic pharmacokinetic parameters in the Torasemide 5 mg group were the following [mean PR/mean IR (90% C.I.)]: Ln AUCO-t=l-03 (0.90-1.17); Ln AUCo~ = 1.03 (0.90-1.16); Ln C_(max)=0.82 (0.68-0.98). The plasmatic pharmacokinetic parameters in the Torasemide 10 mg group were the following [mean PR/mean IR (90% C.I.)]: Ln AUC=1.07 (0.99-1.14); Ln AUC_0 = 1.07 (0.99-1.14); Ln C_(max):=0.68 (0.60-0.78). There were no differences between Torasemide-PR and Torasemide-IR in total volume of urine and electrolyte excretion. There were more episodes of acute diuresis with Torasemide-PR in the 5 mg group and with Torasemide-IR in the 10 mg group. No significant adverse events were reported.Conclusions: Both Torasemide formulations showed similar systemic exposures represented by AUC values within the bioequival-ence 90% C.I. acceptance criteria (0.80-1.25). Peak of plasmatic concentrations (C_(max)) were significantly lowerwith Torasemide-PR than with Torasemide IR . Both formulations where well tolerated and presented a good safety profile.