title: Pharmacokinetics, Safety and Cognitive Function Profile of Rupatadine 10, 20 and 40 mg in Healthy Japanese Subjects: A Randomised Placebo-Controlled Trial.
abstract: BACKGROUND
  Rupatadine is a marketed second generation antihistamine, with anti-PAF activity, indicated for symptomatic treatment of allergic rhinitis and urticaria. This study was conducted to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of rupatadine in healthy Japanese subjects after single and multiple oral doses.
  
  
  METHODS
  In this randomised, double-blind, placebo-controlled study, 27 male and female healthy Japanese subjects were administered single and multiple escalating rupatadine dose of 10, 20 and 40 mg or placebo. Blood samples were collected at different time points for PK measurements and subjects were assessed for safety and tolerability. The effect of rupatadine on cognitive functioning was evaluated by means of computerized cognitive tests: rapid visual information processing (RVP), reaction time (RT), spatial working memory (SWM) and visual analogue scales (VAS).
  
  
  RESULTS
  Exposure to rupatadine as measured by Cmax and AUC was found to increase in a dose dependent manner over the dose range of 10-40 mg for both single and multiple dose administration. The safety assessments showed that all treatment related side effects were of mild intensity and there were no serious adverse events (SAEs) or withdrawals due to treatment-emergent adverse events (TEAEs) in this study. The therapeutic dose of rupatadine did not show any CNS impairment in any of the cognitive tests.
  
  
  CONCLUSIONS
  This study demonstrated that rupatadine is safe and well tolerated by Japanese healthy subjects. The PK-PD profile confirmed previous experience with rupatadine.
authors.affiliation: Richmond Pharmacology Ltd, St George's University of London, Cranmer Terrace, London, United Kingdom.
authors.forename: Jörg
authors.initials: J
authors.lastname: Täubel
authors.affiliation: Statistik Georg Ferber GmbH, Cagliostrostrasse, Riehen, Switzerland.
authors.forename: Georg
authors.initials: G
authors.lastname: Ferber
authors.affiliation: Richmond Pharmacology Ltd, St George's University of London, Cranmer Terrace, London, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Fernandes
authors.affiliation: Richmond Pharmacology Ltd, St George's University of London, Cranmer Terrace, London, United Kingdom.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lorch
authors.affiliation: J. Uriach y Compañía, S.A., Avda. Camí Reial, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Santamaría
authors.affiliation: J. Uriach y Compañía, S.A., Avda. Camí Reial, Barcelona, Spain.
authors.forename: Iñaki
authors.initials: I
authors.lastname: Izquierdo
mesh_terms: D000328:Adult; D019540:Area Under Curve; D003071:Cognition / Q000187:drug effects*; D003533:Cyproheptadine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006633:Histamine Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007564:Japan; D008297:Male; D010919:Placebos; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors
chemical_list: D006633:Histamine Antagonists; D010919:Placebos; D010972:Platelet Activating Factor; C103639:rupatadine; D003533:Cyproheptadine