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Systemic effect comparisons of six inhaled corticosteroid preparations
Richard J Martin1, Stanley J Szefler, Vernon M Chinchilli
1National Jewish Medical and Research Center, Denver, Colorado 80206, USA. martinr@njc.org
Summary
This study established a method to compare inhaled corticosteroids (ICS) by their systemic effects, finding significant differences in cortisol suppression between various ICS formulations. This allows for more accurate efficacy evaluations beyond arbitrary microgram dosing.
Area of Science:
- Pharmacology
- Endocrinology
- Respiratory Medicine
Background:
- Systemic bioavailability and effects of inhaled corticosteroids (ICS) are crucial for asthma management.
- Current methods for comparing ICS efficacy often rely on arbitrary microgram dosing, potentially misrepresenting therapeutic equivalence.
- Establishing equisystemic effects, specifically cortisol suppression, provides a more reliable basis for comparison.
Purpose of the Study:
- To develop a reliable method for evaluating the systemic bioavailability of ICS.
- To determine the equisystemic effects, defined as the microgram dose causing equal systemic cortisol suppression, for various ICS.
- To compare the efficacy of different ICS formulations based on their cortisol suppression potential.
Main Methods:
- A 1-week doubling dose study design was employed in 156 steroid-naive asthma subjects across six centers.
- Systemic effects were assessed using hourly plasma cortisol concentrations, 12- and 24-hour urine cortisol, and morning blood osteocalcin levels.
- The area under the concentration-time curve for plasma cortisol was identified as the optimal variable for assessing systemic effects.
Main Results:
- Six ICS formulations (beclomethasone-CFC, budesonide DPI, fluticasone DPI, fluticasone-CFC MDI, flunisolide-CFC, triamcinolone-CFC) and their placebos were evaluated.
- Only the placebo and fluticasone DPI groups did not show a significant dose-response effect on cortisol suppression.
- Equisystemic doses (micrograms for 10% cortisol suppression) varied widely: flunisolide-CFC (936), triamcinolone-CFC (787), beclomethasone-CFC (548), fluticasone DPI (445), budesonide DPI (268), and fluticasone-CFC MDI (111).
Conclusions:
- This study provides the first evaluation of ICS efficacy based on equisystemic cortisol suppression.
- Significant differences in systemic effects exist among ICS, even when doses are not directly comparable on a microgram basis.
- The findings support a shift towards comparing ICS based on their actual systemic impact rather than arbitrary microgram amounts for improved clinical decision-making.