[Effectiveness and safety of fluticasone propionate in therapy of children suffering from asthma. Part I. Mechanisms of actions and clinical effectiveness of treatment in children with asthma]

Abstract

The introduction of inhaled corticosteroids (ICS) has been a milestone in asthma therapy. According to current guidelines ICS are the first line drug in chronic anti-inflammatory therapy. The purpose of first part of this publication is to present updated knowledge on mechanisms of anti-inflammatory action as well as some pharmacokinetics and pharmacodynamics data about commonly used ICS, especially fluticasone propionate (FP) and two others: budesonide (BUD), beclomethasone dipropionate (BDP). Some differences between mentioned drugs have been found concerning systemic activity and safety of therapy. Fluticasone propionate is twice as active as the BUD and BDP. First results of therapy are seen 1-2 week after administration. Fluticasone propionate, more lipophilic than other steroids, has also high glucocorticoid receptor affinity and specificity, high topical anti-inflammatory activity and low systemic bioavailability. Systemic availability of FP depends on absorption from respiratory system. Oral bioavailability can be neglected because of almost total inactivation in liver during first pass. Fluticasone propionate has some features of dissociated steroids which means predominance of transrepression over transactivation--beneficial from safety point of view. Clinical efficacy of FP in chronic asthma therapy in children was confirmed in many studies. It significantly reduces the symptoms and exacerbations of asthma. There is a close correlation between FP use and lung function tests. The therapy with FP decreases bronchial hyperreactivity and the use of systemic steroids and rescue medication. The beneficial action of fluticasone propionate in asthma is due its anti-inflammatory properties within the airways (decreasing levels of direct and indirect markers of airways inflammations are observed).