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  Authority of Polish Society of Allergology

vol 13. no 3. September 2008  

 Review articles
Selected pharmacokinetic parameters in inhaled glucocorticosteroids safety evaluation

Inhaled glucocorticosteroids (ICS) remain the main treatment In asthma. They exert their action via highly specific cytoplasmatic receptors. Binding of a CS molecule to the receptor starts two effects: genetic pathway (or trans-activation) requiring migration of CS-receptor complex into the cell nucleus and direct interaction with histones and DNA – this pathway produces most unwanted effects of CS action. The second effect – non-genetic pathway (or trans-represion) occurs via transcription factor inactivation in cytoplasm. This pathway is responsible for inhibition most pro-inflammatory cytokines production. In the future separate regulation of both pathway may stand for an important change in ICS pharmacokinetics and pharmacodynamics. At present more “classical” parameters seem to play roles. ICS should stay within pulmonary tissue for as long as possible and present a good penetration to its receptor. It’s well known that receptor affinity is clinically of minor importance since most documents (including GINA) present tables of equivalent doses based on this parameter. Outside of pulmonary tissue safety of ICS is increased by: high effect of first hepatic passage, high plasma protein binding ratio, low volume of distribution and high clearance. Author discusses these parameters in context of differences between ICS available.

keywords: wziewne glikokortykosteroidy, farmakokinetyka, objętość dystrybucji, bezpieczeństwo, inhaled glukocorticosteroids, pharmacokinetics, volume of distribution, safety

pages: from 147 to 150

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