Clinical Potencies of Glucocorticoids: What do we Really Measure?
Emile F.L. Dubois.
Glucocorticoids (GC) are used in pulmonary medicine since the early nineteen-thirties; in the beginning by using extracts of adrenal glands of animals, later on synthetically composed and since the early nineteen-seventies in inhaled formulation. In pulmonary medicine the majority of prescriptions are related to asthma and exacerbations of COPD. In determining the pharmacological potency of the different GCs many efforts were made for quantification. In this respect in vitro, in vivo, ex vivo and clinical studies were performed. Examples in estimating the GC potency range from skin-blanching tests to suppressive effect on the adrenal gland, the latter representing a classical paradigm. Thus far different quantifying attempts that have been made did not take into account the tissue concentration-effect relationship, which can be achieved by pharmacokinetic / pharmaco-dynamic (PK / PD) modelling. Moreover, in the clinical studies described, the suggestion was risen that GCs may have a different potency towards each target tissue separately and that the suppressive effect on the adrenal gland does not reflect for instance its anti-inflammatory action. In this respect the studies describe a quantifying inflammation model for asthma e.g. by granulocyte colony stimulating factor (GCSF) stimulated rise in eosinophilic cationic protein (ECP), which could be inhibited by different GCs. In conclusion, studies on potencies of GC should comprise PK / PD modelling and should target as much as possible on the different outcome parameters of the therapeutical and adverse effects separately and simultaneously, thereby describing the spectrum of potency of a GC rather than the potency.
Keywords: adrenal gland, corticosteroids, inflammation, lymphocyte, cytokine
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