GLUCOCORTICOID PHARMACOKINETICS - 08/09/11

Doi : 10.1016/S0889-8561(05)70118-1

Joseph D. Spahn, MD ^{^{*
Ira J. and Jacqueline Neimark Laboratory of Clinical Pharmacology in Pediatrics, Divisions of Clinical Pharmacology and Allergy–Clinical Immunology, Department of Pediatrics, National Jewish Medical and Research Center; and the Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado}}

Résumé

Glucocorticoids (GC), administered topically or systemically, form the cornerstone of asthma therapy. Delivered systemically, GCs serve as a major component of rescue therapy for acute asthma exacerbations. They also serve as chronic supplemental therapy in patients with severe persistent asthma who remain symptomatic despite high-dose inhaled GC therapy. Inhaled GCs are now the preferred controller medication for all asthmatics except for those with the mildest disease.

Glucocorticoids have been used in the treatment of asthma for nearly 50 years, beginning soon after cortisone was first synthesized and following reports that cortisone and corticotropin were effective in the treatment of rheumatoid arthritis.^{34 Hench P.S., Kendall E.C., Slocomb C.H. , et al. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone: compound E) and of pituitary adrenocorticotropic hormone on rheumatoid arthritis; preliminary report Proceedings of the Staff Meetings of the Mayo Clinic 1949 ; 24 : 181

Cliquez ici pour aller à la section Références} The early studies with cortisone showed improvements in asthma symptoms and pulmonary function and reductions in the numbers of circulating lymphocytes and eosinophils.^{11 Carryer H.M., Koelsche G.A., Prickman L.E. , et al. The effect of cortisone on bronchial asthma and hay fever occurring in subjects sensitive to ragweed pollen Journal of Allergy 1950 ; 21 : 282-287 [cross-ref]

Cliquez ici pour aller à la section Références, 27 Feinberg S.M., Dannenberg T.B., Malkiel S. ACTH and cortisone in allergic manifestations: Therapeutic results and studies on immunological and tissue reactivity Journal of Allergy 1951 ; 22 : 195-210 [cross-ref]

Cliquez ici pour aller à la section Références, 57 Randolph T.G., Rollins J.P. The effect of cortisone on bronchial asthma Journal of Allergy 1950 ; 21 : 288-295 [cross-ref]

Cliquez ici pour aller à la section Références} Since then, great strides have been made in the understanding of how GCs act at the molecular and cellular level and also in the awareness of the multitude of adverse effects associated with prolonged use of GCs. Inhaled GC preparations have been developed that, because of their high topical-to-systemic effects, have proven to be safe and very effective in the treatment of asthma. This article provides a broad overview of the structure, pharmacokinetics, and pharmacodynamics of both systemically administered and inhaled GCs.