A P Baptist1, R C Reddy. 1. Division of Allergy and Clinical Immunology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
Abstract
OBJECTIVES: To assess similarities and differences among currently available inhaled corticosteroids (ICS) for treatment of asthma, with special emphasis on factors that may affect the relative safety of these medications. METHODS: PubMed was searched for relevant reviews and original articles. Information from these studies was synthesized and critically assessed. RESULTS: Differences in corticosteroid formulations and delivery systems can create variations in therapeutic efficacy. Chemical properties of the various corticosteroids may also affect their relative safety. Ciclesonide and beclomethasone dipropionate are administered as prodrugs activated by enzymes present in the lungs but not the oropharynx. Corticosteroid-specific adverse effects in the oropharynx are thus avoided, although formulation-specific effects may remain. Other adverse effects require systemic availability, either via the gastrointestinal tract or the lung. Once they enter the systemic circulation, all ICS are rapidly metabolized by the liver. Oral bioavailability of ICS such as fluticasone, ciclesonide and mometasone is minimal, as a result of their essentially complete first-pass metabolism in the liver. Ciclesonide also undergoes extrahepatic metabolism that eliminates it even more rapidly. Additionally, ciclesonide and mometasone exhibit very high levels of binding to serum proteins that reduces their ability to stimulate glucocorticoid receptors outside the lung. CONCLUSIONS: Despite acting by similar mechanisms, currently available ICS and their delivery systems differ in ways that can potentially affect both safety and therapeutic effectiveness for individual patients.
OBJECTIVES: To assess similarities and differences among currently available inhaled corticosteroids (ICS) for treatment of asthma, with special emphasis on factors that may affect the relative safety of these medications. METHODS: PubMed was searched for relevant reviews and original articles. Information from these studies was synthesized and critically assessed. RESULTS: Differences in corticosteroid formulations and delivery systems can create variations in therapeutic efficacy. Chemical properties of the various corticosteroids may also affect their relative safety. Ciclesonide and beclomethasone dipropionate are administered as prodrugs activated by enzymes present in the lungs but not the oropharynx. Corticosteroid-specific adverse effects in the oropharynx are thus avoided, although formulation-specific effects may remain. Other adverse effects require systemic availability, either via the gastrointestinal tract or the lung. Once they enter the systemic circulation, all ICS are rapidly metabolized by the liver. Oral bioavailability of ICS such as fluticasone, ciclesonide and mometasone is minimal, as a result of their essentially complete first-pass metabolism in the liver. Ciclesonide also undergoes extrahepatic metabolism that eliminates it even more rapidly. Additionally, ciclesonide and mometasone exhibit very high levels of binding to serum proteins that reduces their ability to stimulate glucocorticoid receptors outside the lung. CONCLUSIONS: Despite acting by similar mechanisms, currently available ICS and their delivery systems differ in ways that can potentially affect both safety and therapeutic effectiveness for individual patients.
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