TDM11 FOOD INTERACTION BIOAVAILABILITY STUDY OF A TORASEMIDE NEW FORMULATION (10 MG PROLONGED RELEASE) AFTER A HIGH FAT CONTENT MEAL

摘要

Objectives: To evaluate the effect of food interaction in the bioavail-ability of a new prolonged release formulation of Torasemide (Tora-semi de-PR).Setting: Intra-hospital Phase-I Unit.Methods: The food interaction effect on bioavailability of a new prolonged release formulation of Torasemide was evaluated in a single-dose, randomized, 3-way cross-over, clinical trial. The study included 18 healthy volunteers who received one administration of 10 mg Torasemide immediate release (IR) in fasting conditions (IR-F), one administration of 10 mg Torasemide-PR in fasting conditions (PR-F) and one administration of 10 mg Torasemide-PR after a high fat content meal (PR-M). Each administration was separated by a minimum of 7 days wash-out period. Blood samples were obtained for determination of pharmacokinetic parameters. Safety and tolerability were also assessed.Results: The main results of the analysis of the plasmatic pharmacokinetic parameters are the following. 1) mean PR-F/mean 1R-F (90% C.I.):LnAUC_(0-t)=101.18 (92.64-110.50); Ln AUC0_ = 101.20 (92.66-110.52); Ln C_(max)=67.48 (55.34-82.29) . 2) mean PR-M/ mean PR-F (90% C.I.): Ln AUC_(0-t)=89.04 (81.52-97.24); Ln AUC0 ,,=89.06 (81.55-97.27); Ln C_(max)=79.07 (64.84-96.43). No significant adverse events were reported.Conclusions: When administered in fasting conditions, both Torasemide formulations showed similar systemic exposures represented by AUC values within the bioequivalence 90% C.I. acceptance criteria (80-125%). Torasemide PR C_(max)values were statistically significant lower than Torasemide IR C_(max)values. When administered after a high fat content meal, Torasemide-PR shows a reduction in C_(max)in relation to its administration in fasting conditions; although, the systemic exposure (AUCs) remains within the bioequivalence 90% C.I. acceptance criteria (80-125%). Both formulations where well tolerated and presented a good safety profile.