Antihistaminic effects of rupatadine and PKPD modelling

Eur J Drug Metab Pharmacokinet. 2008 Apr-Jun;33(2):107-16. doi: 10.1007/BF03191027.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Biotransformation
  • Cyproheptadine / analogs & derivatives*
  • Cyproheptadine / pharmacokinetics
  • Cyproheptadine / pharmacology
  • Female
  • Histamine Antagonists / pharmacokinetics*
  • Histamine Antagonists / pharmacology*
  • Humans
  • Loratadine / blood
  • Male
  • Models, Statistical
  • Population
  • Sex Factors


  • Histamine Antagonists
  • rupatadine
  • Cyproheptadine
  • Loratadine