Systemic bioactivity profiles of oral prednisolone and nebulized budesonide in adult asthmatics.
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.


METHODS
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.
Wilson
A M
AM
Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee, Scotland, UK.
McFarlane
L C
LC
Lipworth
B J
BJ
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood*; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D009330:Nebulizers and Vaporizers; D015675:Osteocalcin / Q000097:blood; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D015675:Osteocalcin; D019819:Budesonide; D011239:Prednisolone; D006854:Hydrocortisone