Antihistaminic effects of rupatadine and PKPD modelling

SummaryRupatadine 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.

[1]  Y. Horsmans,et al.  Pharmacokinetic-Pharmacodynamic Relationships of H1-Antihistamines , 1995, Clinical pharmacokinetics.

[2]  Cockcroft Dw,et al.  Prediction of Creatinine Clearance from Serum Creatinine , 1976 .

[3]  P. Rosenzweig,et al.  Pharmacokinetic and pharmacodynamic modeling of mizolastine in healthy volunteers with an indirect response model , 2000, Clinical pharmacology and therapeutics.

[4]  B. Ganem,et al.  A pharmacokinetic-pharmacodynamic modelling of the antihistaminic (H1) effects of cetirizine. , 1999, International journal of clinical pharmacology and therapeutics.

[5]  I. Izquierdo,et al.  A randomized, double-blind, parallel-group study, comparing the efficacy and safety of rupatadine (20 and 10 mg), a new PAF and H1 receptor-specific histamine antagonist, to loratadine 10 mg in the treatment of seasonal allergic rhinitis. , 2004, Journal of investigational allergology & clinical immunology.

[6]  S. Keam,et al.  Rupatadine , 2012, Drugs.

[7]  E. Arnáiz,et al.  Effects of rupatadine vs placebo on allergen-induced symptoms in patients exposed to aeroallergens in the Vienna Challenge Chamber. , 2006, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[8]  A. Zechnich,et al.  Second-generation antihistamines: a comparative review. , 1999, Drugs.

[9]  C. Picado,et al.  Rupatadine 10 mg and ebastine 10 mg in seasonal allergic rhinitis: a comparison study , 2004, Allergy.

[10]  M. Barbanoj,et al.  Central and Peripheral Evaluation of Rupatadine, a New Antihistamine/Platelet-Activating Factor Antagonist, at Different Doses in Healthy Volunteers , 2004, Neuropsychobiology.

[11]  J. García-Rafanell,et al.  Rupatadine, a new potent, orally active dual antagonist of histamine and platelet-activating factor (PAF). , 1997, The Journal of pharmacology and experimental therapeutics.

[12]  A. Zechnich,et al.  Second-Generation Antihistamines , 2012, Drugs.

[13]  E. Arnáiz,et al.  Rupatadine 10 mg and cetirizine 10 mg in seasonal allergic rhinitis: a randomised, double-blind parallel study. , 2005, Journal of investigational allergology & clinical immunology.