Rupatadine does not potentiate the CNS depressant effects of lorazepam: randomized, double-blind, crossover, repeated dose, placebo-controlled study.
OBJECTIVE
The main objective was to assess whether benzodiazepine intake when rupatadine plasma concentrations were at steady-state would increase the CNS depressant effects. Rupatadine is a new H(1)-antihistamine which also inhibits platelet activating factor (PAF) release and has been shown to be clinically effective at doses of 10 mg.


METHODS
Sixteen healthy young volunteers took part in a crossover, randomized, double-blind, placebo controlled trial comprising two experimental periods (repeated administration for 7 days of rupatadine 10 mg or placebo as single oral daily doses, separated by a washout of 14 days). On days 5 and 7, according to a fully balanced design, a single oral dose of lorazepam 2 mg or placebo was added. CNS effects were evaluated on these days by seven objective tests of psychomotor performance and eight subjective visual analogue scales (VAS) at pre-dose and several times after drug intake. Four treatment conditions were evaluated: placebo, rupatadine 10 mg, lorazepam 2 mg and rupatadine 10 mg + lorazepam 2 mg.


RESULTS
Significant CNS effects, either impairment of psychomotor performance or subjective sedation, were observed when lorazepam was administered, either alone or in combination with steady state concentrations of rupatadine. No significant differences were found between these two conditions. In addition, rupatadine was not different from placebo. All treatments were well tolerated.


CONCLUSIONS
Repeated doses of rupatadine (10 mg orally) did not enhance the CNS depressant effects of lorazepam (2 mg orally, single dose) either in objective psychomotor tasks or in subjective evaluations.
García-Gea
Consuelo
C
Centre d'Investigació de Medicaments, (CIM-Sant Pau), Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau (HSCSP), Barcelona, Spain.
Ballester
Maria Rosa
MR
Martínez
Juan
J
Antonijoan
Rosa Maria
RM
Donado
Esther
E
Izquierdo
Iñaki
I
Barbanoj
Manuel-José
MJ
D000328:Adult; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018592:Cross-Over Studies; D003533:Cyproheptadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*
D002492:Central Nervous System Depressants; D004338:Drug Combinations; D006634:Histamine H1 Antagonists; C103639:rupatadine; D003533:Cyproheptadine; D008140:Lorazepam