Pharmacological profile, efficacy and safety of rupatadine in allergic rhinitis

Abstract

Allergic rhinitis (AR) is a disease with high prevalence. In AR, exposure to airborne allergens elicits an allergic response which involves epithelial accumulation of effector cells -e.g. mast cells and basophils -and subsequent inflammation. During the early response in AR, histamine has been found to be the most abundant mediator and it is associated with many symptoms of this disease mediated through the histamine H1 receptor. Therefore, anti-histamines have a role to play in the management of AR. However, the available antihistamines have certain well-known side effects like sedation and potential pro-arrythmic effects owing to their interactions with other drugs, as well as having poor or no effect on platelet activating factor (PAF) which also plays an important role in AR. This article is a qualitative systematic literature review on the pharmacological profile of rupatadine in order to evaluate its safety and efficacy in AR as compared to other anti-histamines. Rupatadine is a once-daily non-sedative, selective, long-acting H1 anti-histamine with antagonistic PAF effects through its interaction with specific receptors. Rupatadine significantly improves nasal symptoms in patients with AR. It has a good safety profile and is devoid of arrythmogenic effects. These properties make rupatadine a suitable first line anti-histamine for the treatment of AR.

Rupatadine Inhibits Proinflammatory Mediator Secretion from Human Mast Cells Triggered by Different Stimuli

“…Rupatadine is a newer H 1 receptor antagonist [12, 13] with the ability to also inhibit actions of PAF [14, 15]. Rupatadine appears to be more potent than other antihistamines in the treatment of allergic rhinitis [16, 17] and chronic idiopathic urticaria [18,19,20].…”

Assessment of polymorphic metabolite data in bioavailability/bioequivalence studies - considerations and challenges

“…[13] While literature citations that implicated rupatadine as a polymorphic substrate were not readily found, interestingly a recent review article on rupatadine that included clinical pharmacology and metabolism attributes claimed that it was unlikely that rupatadine would be a substrate for polymorphic CYP isozymes. [14] However, Solans et al (2008) provided a hint that there was a genetic variability in the pharmacokinetic parameters in earlier studies for desloratadine [15,16] and pointed out that the formation of 3-hydroxyloratadine metabolite from desloratadine was under the control of genetic polymorphism. [13,15,16] Interestingly, the CYP enzyme responsible for the formation of 3-hydroxyloratadine has not been identified.…”

“…Additionally, the existence of such genetic polymorphism may go unnoticed for considerable time due to lack of appropriate study population as evidenced by lack of literature citations on this aspect of rupatadine's metabolism until recently. [14,17] While more publications of these types of DDI studies would provide a strong base to appreciate the complexities involved in the polymorphic metabolism of primary metabolite(s), it is prudent to adopt a study design that provides the right balance in achieving the study objectives if existence of polymorphic metabolism is suspected in the disposition of primary metabolite without risking a study failure to unsuspected "polymorphic" metabolism.…”

Unsuspected polymorphic metabolism of rupatadine via its primary metabolite, desloratadine

“…In their systematic review published in this issue of the Primary Care Respiratory Journal, 1 Katiyar and Prakash have extensively and eloquently summarised the clinical pharmacology and metabolism characteristics -including the safety and efficacy parameters -of rupatadine in the treatment of allergic rhinitis. However, while their systematic review is thorough and provides perspectives and guidance for the effective use of rupatadine, it inadvertently does not mention the latest data with regard to genetic polymorphism in the metabolic disposition of rupatadine which may have significance in the clinical treatment options.…”

“…2 Since the impact of genetic polymorphism has been well documented across different therapeutic areas, 6 this interesting observation on rupatadine's primary metabolite disposition raises important questions. Firstly, the notion that rupatadine is not subject to polymorphic metabolism like some other compounds in the class 1,7 should be viewed with caution, since the primary metabolite (i.e. desloratadine) is a substrate for polymorphic metabolism.…”