EC14 LACK OF PHARMACODYNAMIC INTERACTION BETWEEN RUPATADINE AND A DEPRESSANT OF THE CNS: CROSSOVER, RANDOMIZED, DOUBLE BLIND AND PLACEBO CONTROLLED CLINICAL TRIAL IN YOUNG HEALTHY VOLUNTEERS

摘要

Objectives: To evaluate if the treatment with rupatadine potentiates the CNS depressant effects of benzodiazepines (lorazepam). Tolera-bility was also assessed.Setting: Intra-hospital Phase I Unit.Method: Eighteen healthy volunteers were recruited and 16 analyzed in this double-blind, crossover trial that comprised two randomized treatment periods, with 2 week washout between them. Rupatadine (RU)10 mg tablet qd orally or placebo (Pb) were given during 7 days. On days 5 and 7 of each treatment period, a single oral dose of lorazepam (LZ) 2 mg or Pb was coadministered in a randomized balanced schedule. The effects on the CNS were evaluated by analyzing the changes from baseline induced in objective tests (tapping test, flicker fusion frequency, "d2" cancellation test, multiple reaction time test, two-hand coordination test, Pauli test and visual recognition test) and in subjective tests (visual analogue scales) at different time points, particularly in Tmax 1.5 h.Results: In the psychomotor performance tests, a significant impairment was found when LZ was administered, with no differences being found between LZ administration alone or LZ administration together with repetitive RU admistration: reductions in the number of strikes/second, in flicker-fusion threshold, in the total number and in the number of symbols correctly cancelled and in the number of calculations performed; increase in the time used to respond to complex stimuli. In the subjective evaluation questionnaires, a similar profile of effects was obtained. The subjects reported to be more drowsy, dull, clumsy, passive, inattentive and incompetent when LZ was administered (as single dose or as added dose with repetitive RU administration). In the overall analysis of residual effects, not significant differences between Pb and RU repeated treatments regimes were found. All treatments were well tolerated.Conclusions: Steday-state rupatadine plasma concentrations does not potentiate the depressant CNS effects of benzodiazepines, throught neither objetive psychomotor tasks nor subjective evaluations.