title: Influence of food on the oral bioavailability of rupatadine tablets in healthy volunteers: a single-dose, randomized, open-label, two-way crossover study.
abstract: BACKGROUND
  Rupatadine is an oral active antihistamine for the management of diseases with allergic inflammatory conditions, such as perennial and seasonal rhinitis and chronic idiopathic urticaria. Oral rupatadine has been approved for the treatment of allergic rhinitis and chronic urticaria in adults and adolescents in several European countries.
  
  
  OBJECTIVE
  The purpose of this study was to describe the effect of the concomitant intake of food on the pharmacokinetic profile and bioavailability of a single dose of rupatadine.
  
  
  METHODS
  This was a single-dose, randomized, open-label, 2-way crossover study in which healthy male and female volunteers received a single, 20-mg oral dose of rupatadine under fed and fasting conditions. Blood samples were collected and plasma concentrations of rupatadine and its active metabolites desloratadine and 3-hydroxydesloratadine were determined by liquid chromatography tandem mass spectrometry. Tolerability was based on the recording of adverse events (AEs), physical examinations, electrocardiograms, and laboratory tolerability tests immediately before each treatment period and at the final visit of the study.
  
  
  RESULTS
  Twenty-four volunteers (12 males; mean [SD] age, 25.4 [5.3] years [range, 18-34 years]; mean [SD] weight, 71.2 [4.3] kg [range, 64-77 kg]; 12 females; mean [SD] age, 26.8 [6.5] years [range, 18-38 years]; mean [SD] weight, 58.4 [6.8] kg, [range 50-69 kg]) were enrolled and randomized with equal distribution of sex. A significant increase in AUC from drug administration to the final quantifiable sample (AUC(0-t)) and AUC from drug administration to infinity (AUC(0-infinity)) values of rupatadine was seen under fed conditions without affecting C(max). The ratios (90% CI) of the mean log-transformed AUC(0-t) and AUC(0-infinity) for rupatadine revealed a significant increase in AUC(0-t) (ratio 131%; 90% CI, 111%-154%) and AUC(0-infinity) (ratio 133%; 90% CI, 113%-156%), whereas C(max) remained unaltered (ratio 97%; 90% CI, 80%-116%). Plasma concentration-time profiles of desloratadine and 3-hydroxydesloratadine were similar with and without food, and no differences were seen for AUC(0-t), AUC(0-infinity), or C(max). Seven (28%) subjects reported > or =1 AE. All AEs were mild, resolved spontaneously, and did not affect the outcome of the study.
  
  
  CONCLUSIONS
  The results of this study indicate that concomitant intake of food with a single 20-mg oral dose of rupatadine exhibits a significant increase in rupatadine bioavailability. Despite the absence of bioequivalence, the drug was well tolerated under fed and fasting conditions, and no major changes in severity and/or prevalence of AEs were reported.
authors: Pharmacokinetic and Bioanalysis Department, J Uriach y Compañía, S.A., Barcelona, Spain. Electronic address: pk-asolans@uriach.com.
authors: Anna
authors: A
authors: Solans
authors: Pharmacokinetic and Bioanalysis Department, J Uriach y Compañía, S.A., Barcelona, Spain.
authors: Marcel Lí
authors: ML
authors: Carbó
authors: Pharmacokinetic and Bioanalysis Department, J Uriach y Compañía, S.A., Barcelona, Spain.
authors: Juana
authors: J
authors: Peña
authors: Pharmacokinetic and Bioanalysis Department, J Uriach y Compañía, S.A., Barcelona, Spain.
authors: Teresa
authors: T
authors: Nadal
authors: Clinical Research Unit, J Uriach y Compañía, S.A., Barcelona, Spain.
authors: Iñaki
authors: I
authors: Izquierdo
authors: Drug Development, J Uriach y Compañía, S.A., Barcelona, Spain.
authors: Manuel
authors: M
authors: Merlos
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003533:Cyproheptadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D018565:Food-Drug Interactions; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D017336:Loratadine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D013607:Tablets
chemical_list: D006634:Histamine H1 Antagonists; D013607:Tablets; C103639:rupatadine; D003533:Cyproheptadine; C482880:3-hydroxydesloratadine; D017336:Loratadine; C121345:desloratadine