Methods and Findings in Experimental and Clinical Pharmacology
Vol. 24, Suppl. A, 2002, pp. 37
ISSN 0379-0355
Copyright 2002 Prous Science, S.A.
CCC: 0379-0355/2002
http://www.prous.com

Rupatadine, a New Nonsedating Antihistamine and PAF Antagonist

M. Merlos

J. Uriach and Cía Research Center

Rupatadine (RU) is a powerful antihistamine H₁-receptor and PAF-receptor antagonist, with prolonged duration of effect after oral administration. RU's antiallergic activity has been assessed in several species (mice, rats, guinea pigs, dogs) and situations (active vs. passive anaphylaxis, systemic vs. topical anaphylaxis). A number of additional activities such as inhibition of mast cell degranulation, effects on neutrophil and eosinophil migration and inhibition of cytokine release may contribute to RU's excellent antiallergic profile. Preclinical toxicology and safety studies evidenced that RU was a well-tolerated drug with a wide safety margin, and this has been further confirmed in clinical trials.

In vitro and in vivo studies did not identify potential for QT prolongation after RU administration. A total of 13 phase I clinical trials have primarily addressed the pharmacodynamics and pharmacokinetics of RU (doses 2-80 mg). The safety and efficacy of RU (mostly 10 and 20 mg once daily) in the treatment of intermittent (IAR) and persistent (PAR) allergic rhinitis has been evaluated in three phase II and seven phase III clinical trials, including a total sample of 2903 subjects (1708 treated with RU). In both IAR and PAR, doses of 10 and 20 mg provided better efficacy than placebo, and similar or superior efficacy than known gold standards. The adverse event profile of RU was similar to that reported for other second-generation antihistamines. No significant influence in the QTc interval has been reported following recent ICH recommendation. Clinical trials in chronic idiopathic urticaria are ongoing. In summary, current available data show that RU 10 mg has a favorable risk/benefit balance representing an effective and safe new option in the management of symptoms associated with allergies.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 24, Suppl. A, 2002, pp. 37
ISSN 0379-0355 Copyright 2002 Prous Science, S.A. CCC: 0379-0355/2002 http://www.prous.com