[show abstract][hide abstract] ABSTRACT: This review aims to compare continuous with on-demand pharmacotherapy of allergic rhinitis by focusing on pharmacodynamic, pharmacokinetic, safety, effectiveness, cost and cost-effectiveness considerations. A working party of experts reviewed and discussed the literature and guidelines, and conducted a qualitative analysis of the Summary of Product Characteristics of specific medicines. With respect to medicines, the working party limited itself to antihistamines, nasal corticosteroids and leukotriene antagonists. Based on a review of the evidence from a multidisciplinary perspective, this article makes pharmacotherapeutic recommendations that are easy, functional and applicable to daily practice in primary care. The pharmacotherapeutic evidence for continuous versus on-demand treatment of allergic rhinitis was limited. Clearly, for corticosteroids, their mechanism of action in allergic rhinitis of reducing allergic inflammation requires continuous therapy at least for the duration of symptoms. For H(1)-antihistamines, some trials suggest that continuous treatment is preferable but more studies are needed to confirm this conclusion. For both H(1)-antihistamines and nasal corticosteroids safety data indicate that continuous treatment may be given without fears of adverse consequences, although a distinction can be made between the first and the second generation antihistamines. With regard to the cost and cost-effectiveness implications of continuous therapy versus on-demand therapy, more studies are necessary before definitive conclusions may be made.
Respiratory medicine 02/2010; 104(5):615-25. · 2.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Second generation H1 antihistamines are considered first-line therapy for allergic rhinitis and chronic idiopathic urticaria, largely because of their nonsedating effects. Evaluating pharmacokinetic and pharmacodynamic parameters and clinical efficacy of a drug is important, but models to predict clinical efficacy are lacking. Receptor occupancy (RO), a predictor for human pharmacodynamics and antihistamine potency that takes into account the affinity of the drug for the receptor and its free plasma concentration, may be a more accurate way to predict a drug's clinical efficacy. This study was designed to assess the concept of RO as a surrogate for clinical efficacy, using examples of second generation oral antihistamines. A literature review was conducted using MEDLINE. Search terms included allergy, allergic rhinitis, drug efficacy, over-the-counter drugs, perennial allergic rhinitis, seasonal allergic rhinitis, second generation antihistamines, chronic idiopathic urticaria, and treatment outcomes. Abstracts and posters from recent allergy-related society meetings were also used. RO of several second generation H1 antihistamines was derived from noncomparative and head-to-head studies. Fexofenadine and levocetirizine showed similar RO at 4 hours, both higher than that of desloratadine. Levocetirizine established higher RO than fexofenadine or desloratadine at 12 and 24 hours. RO for these agents appeared to correlate with pharmacodynamic activity in skin wheal and flare studies and with efficacy in allergen challenge chamber studies. Parameters affecting RO included time from dosing, pH, and dosing regimen. RO did not appear to be linearly related to drug concentration. Results indicate that RO is an accurate predictor of in vivo pharmacodynamic activity and clinical efficacy.
Allergy and Asthma Proceedings 04/2009; 30(4):366-76. · 2.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: Whilst pharmacokinetics describe the relationship between dose levels and concentration-time profiles of a drug in the body and pharmacodynamics describe the concentration-response relationships, pharmacokinectics-pharmacodynamics(PK-PD) models link these two items providing a framework for modelling the time course of drug response. In this chapter, PK-PD models, describing the therapeutic effects of drugs used for the therapy of allergic diseases have been reviewed. Emphasis was given also to the description of the receptor occupancy, which is tightly related to the downstream clinical response. PK - PD models describing unwanted effects were also commented. An integrated use of these models allows choosing appropriate dosing regimens and providing an objective evaluation of the benefit/risk balance.
Drug Metabolism Reviews 02/2009; 41(3):455-74. · 5.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Allergic diseases are characterized by the activation of inflammatory cells and by a massive release of mediators. The aim of this chapter was to describe succinctly the modes of action, indications, and side effects of the major antiallergic and antiasthmatic drugs. When considering the ideal pharmacokinetic characteristics of a drug, a poorly metabolized drug may confer a lower variability in plasma concentrations and metabolism-based drug interactions, although poorly metabolized drugs may be prone to transporter-based disposition and interactions. The ideal pharmacological properties of a drug include high binding affinity, high selectivity, and appropriate association and dissociation rates. Finally, from a patient perspective, the frequency and route of administration are important considerations for ease of use.
Drug Metabolism Reviews 02/2009; 41(3):301-43. · 5.54 Impact Factor