A M Wilson1, L C McFarlane, B J Lipworth. 1. Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee, Scotland, UK.
Abstract
STUDY OBJECTIVE: Because nebulized budesonide may be used as an alternative to maintenance oral prednisolone in the treatment of severe chronic asthma, it is important to compare these two drugs to determine their relative systemic bioactivity profiles in terms of effects on adrenal, bone, and hematologic markers. DESIGN:Twelve asthmatic patients (mean age; 34.7 years; mean FEV1; 88.3% predicted; mean forced expiratory flow between 25% and 75% of FVC, 54.8% predicted) were studied in a double-blind, double-dummy, randomized crossover design to compare placebo, low, medium, and high doses of nebulized budesonide given bid (1, 2, and 4 mg/d, respectively), and oral prednisolone given qd (5, 10, and 20 mg/d). All treatments and both placebos were given for 4 days at each dose level with a 7-day washout period between each treatment block with budesonide or prednisolone. All measurements were made at 8 AM after the last dose of each dose increment for plasma cortisol, serum osteocalcin, and blood eosinophil count. RESULTS: Regression analysis showed significant dose-related suppression with prednisolone for 8 AM plasma cortisol (p<0.0001), osteocalcin (p<0.05), and blood eosinophil count (p<0.0005), but not with budesonide. Compared with placebo, there were significant differences only with prednisolone, at the medium- and high-dose levels for all three markers. CONCLUSIONS: For all three systemic bioactivity markers (8 AM plasma cortisol, serum osteocalcin, and blood eosinophils), there was significant dose-related suppression with prednisolone but not with budesonide. Further long-term studies are required in more severe asthmatics in order to evaluate the therapeutic index.
RCT Entities:
STUDY OBJECTIVE: Because nebulized budesonide may be used as an alternative to maintenance oral prednisolone in the treatment of severe chronic asthma, it is important to compare these two drugs to determine their relative systemic bioactivity profiles in terms of effects on adrenal, bone, and hematologic markers. DESIGN: Twelve asthmatic patients (mean age; 34.7 years; mean FEV1; 88.3% predicted; mean forced expiratory flow between 25% and 75% of FVC, 54.8% predicted) were studied in a double-blind, double-dummy, randomized crossover design to compare placebo, low, medium, and high doses of nebulized budesonide given bid (1, 2, and 4 mg/d, respectively), and oral prednisolone given qd (5, 10, and 20 mg/d). All treatments and both placebos were given for 4 days at each dose level with a 7-day washout period between each treatment block with budesonide or prednisolone. All measurements were made at 8 AM after the last dose of each dose increment for plasma cortisol, serum osteocalcin, and blood eosinophil count. RESULTS: Regression analysis showed significant dose-related suppression with prednisolone for 8 AM plasma cortisol (p<0.0001), osteocalcin (p<0.05), and blood eosinophil count (p<0.0005), but not with budesonide. Compared with placebo, there were significant differences only with prednisolone, at the medium- and high-dose levels for all three markers. CONCLUSIONS: For all three systemic bioactivity markers (8 AM plasma cortisol, serum osteocalcin, and blood eosinophils), there was significant dose-related suppression with prednisolone but not with budesonide. Further long-term studies are required in more severe asthmatics in order to evaluate the therapeutic index.
Authors: Tuomas Jartti; Pasi Lehtinen; Timo Vanto; Tytti Vuorinen; Jaakko Hartiala; Heikki Hiekkanen; Pekka Malmberg; Mika Mäkelä; Olli Ruuskanen Journal: Pediatr Allergy Immunol Date: 2007-06 Impact factor: 6.377