title: Evaluation of the cognitive, psychomotor and pharmacokinetic profiles of rupatadine, hydroxyzine and cetirizine, in combination with alcohol, in healthy volunteers.
abstract: BACKGROUND
  The Central Nervous System (CNS) impairment induced by moderate alcohol (ALC) ingestion may be enhanced if other drugs are taken simultaneously. Rupatadine (RUP) is a new H(1)-antihistamine which also inhibits platelet activating factor (PAF) release in inflammatory reactions.
  
  
  OBJECTIVE
  The main aim of the study was to assess the effects of ALC 0.8 g/Kg on RUP (10 mg and 20 mg) CNS effects. An evaluation of alcohol and RUP pharmacokinetics was also attained.
  
  
  METHODS
  Eighteen healthy young volunteers of both sexes participated in a phase I, randomised, crossover, double-blind, placebo-controlled study. At 2-week intervals they received six treatments: (a) placebo (PLA), (b) ALC alone and ALC in combination with: (c) hydroxyzine 25 mg (HYD), (d) cetirizine 10 mg (CET), (e) RUP 10 mg or (f) RUP 20 mg. At baseline and several times thereafter, seven psychomotor performance tests (finger tapping, fine motoric skills, nystagmus, temporal estimation, critical-flicker-fusion frequency, 'd2' cancellation, simple reaction) and eleven subjective self-reports (drunkenness, sleepiness, alertness, clumsiness, anger, inattentiveness, efficiency, happiness, hostility, interest and extraversion) were carried out. Two-way (treatment, time) ANOVAs for repeated measures to each variable together with a multivariate non-parametric approach were applied. Plasma concentrations of alcohol, and of RUP and its metabolites, were quantified by validated immunofluorescence and LC/MS/MS methods, respectively. Plasma-time curves for all compounds were analysed by means of model-independent methods.
  
  
  RESULTS
  The combination of alcohol with HYD, CET and RUP 20 mg produced more cognitive and psychomotor impairment as compared to alcohol alone, being the combination of alcohol and HYD the one which induced the greatest deterioration. The combination of alcohol and RUP 10 mg could not be differentiated from ALC alone. Subjective self-reports reflect effects on metacognition after the combination of alcohol with HYD and CET i.e. the increased objective impairment observed was not subjectively perceived by the subjects. No significant differences were obtained when comparing alcohol plasma concentrations assessed after the treatments evaluated. RUP showed a lineal kinetic relationship after 10 and 20 mg with a higher exposition to both metabolites assayed.
  
  
  CONCLUSIONS
  Present results showed that single oral doses of rupatadine 10 mg in combination with alcohol do not produce more cognitive and psychomotor impairment than alcohol alone. Higher doses of rupatadine, in combination with alcohol, may induce cognitive and psychomotor deterioration as hydroxyzine and cetirizine at therapeutic doses.
authors.affiliation: Centre d'Investigació de Medicaments, Institut de Recerca, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, HSCSP, Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Spain. mbarbanoj@santpau.es
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Barbanoj
authors.forename: Consuelo
authors.initials: C
authors.lastname: García-Gea
authors.forename: Rosa
authors.initials: R
authors.lastname: Antonijoan
authors.forename: Iñaki
authors.initials: I
authors.lastname: Izquierdo
authors.forename: Ester
authors.initials: E
authors.lastname: Donado
authors.forename: Iñaki
authors.initials: I
authors.lastname: Pérez
authors.forename: Anna
authors.initials: A
authors.lastname: Solans
authors.forename: Francesc
authors.initials: F
authors.lastname: Jané
mesh_terms: D000704:Analysis of Variance; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D017332:Cetirizine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D003533:Cyproheptadine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006634:Histamine H1 Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D006919:Hydroxyzine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D004338:Drug Combinations; D006634:Histamine H1 Antagonists; C103639:rupatadine; D003533:Cyproheptadine; D006919:Hydroxyzine; D000431:Ethanol; D017332:Cetirizine