title: Antihistaminic effects of rupatadine and PKPD modelling.
abstract: Rupatadine is a new oral antihistaminic agent used for the management of allergic inflammatory conditions, such as rhinitis and chronic urticaria. The aim of the present study was to develop a population pharmacokinetic/pharmacodynamic (PKPD) model for the description of the effect of rupatadine and one of its active metabolites, desloratadine, on the histamine-induced flare reaction and to predict the response to treatment after repeated administrations of rupatadine. Both rupatadine and desloratadine were characterized by two-compartmental kinetics. For both compounds, covariates sex and weight had a significant effect on several parameters. The pharmacodynamics were described by an indirect model for the inhibition of flare formation that accounted for the contribution of both rupatadine and desloratadine to the antihistaminic effect. The final PKPD model adequately described the original data. The simulated response after repeated once-daily administrations of 10 mg rupatadine showed a significant and maintained antihistaminic effect over time, between two consecutive dosing intervals.
authors.affiliation: Pharmacokinetic & Bioanalysis Department, Palau Pharma SA, Barcelona, Spain.
authors.forename: Juana
authors.initials: J
authors.lastname: Peña
authors.forename: Marcel Li
authors.initials: ML
authors.lastname: Carbo
authors.forename: Anna
authors.initials: A
authors.lastname: Solans
authors.forename: Teresa
authors.initials: T
authors.lastname: Nadal
authors.forename: Iñaki
authors.initials: I
authors.lastname: Izquierdo
authors.forename: Manuel
authors.initials: M
authors.lastname: Merlos
mesh_terms: D000328:Adult; D000465:Algorithms; D001711:Biotransformation; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006633:Histamine Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D017336:Loratadine / Q000097:blood; D008297:Male; D015233:Models, Statistical; D011153:Population; D012737:Sex Factors
chemical_list: D006633:Histamine Antagonists; C103639:rupatadine; D003533:Cyproheptadine; D017336:Loratadine
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