Comparison of the antiasthmatic, oropharyngeal, and systemic glucocorticoid effects of budesonide administered through a pressurized aerosol plus spacer or the Turbuhaler dry powder inhaler

• Published in: Journal of allergy and clinical immunology Vol. 99; no. 2; pp. 186 - 193
• Main Authors: Toogood, John H., White, Frederick A., Baskerville, Jon C., Fraher, Lawrence J., Jennings, Barbara
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-02-1997; Elsevier
• Subjects: Administration, Inhalation; Adult; Aerosols - administration & dosage; Aerosols - pharmacokinetics; Aged; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacokinetics; Anti-Inflammatory Agents - therapeutic use; Asthma; Asthma - blood; Asthma - drug therapy; Biological and medical sciences; Budesonide; Candidiasis, Oral - microbiology; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Delivery Systems - methods; dry powder inhalers; Eosinophils; Female; Humans; Hydrocortisone - blood; Hydrocortisone - urine; inhaled steroids; Lung - drug effects; lung deposition; Male; Medical sciences; Middle Aged; Nebuhaler; Nebulizers and Vaporizers; Osteocalcin - blood; Pharmacology. Drug treatments; Pregnenediones - administration & dosage; Pregnenediones - pharmacokinetics; Pregnenediones - therapeutic use; Respiratory Function Tests; Respiratory system; spacers; Turbuhaler; lung deposition; CL; Turbuhaler; dry powder inhalers; Asthma; budesonide; ANCOVA; MLPF; UFC 24; pMDI; spacers; Nebuhaler; inhaled steroids; Human; Delivery system; Corticosteroid; Budesonide; Respiratory disease; Toxicity; Lung; Antiinflammatory agent; Glucocorticoid; Powder; Inhalation; Chemotherapy; Treatment; Complication; Obstructive pulmonary disease; Effective dose; Aerosol batcher; Deposition; Comparative study
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/S0091-6749(97)70094-0

To determine therapeutically and systemically equivalent dosages of budesonide inhaled through the Turbuhaler dry powder inhalation device (Astra Pharma Production AB, Södertälje, Sweden) or pressurized metered-dose inhaler (pMDI) plus Nebuhaler spacer (Astra Pharma Production AB), we compared these devices in a randomized, open, parallel-group trial. Adults with moderate to severe asthma inhaled budesonide (0.4, 0.8, 1.6, and 2.4 mg/day), for 2 weeks at each dose level, through the Turbuhaler (
n = 30) or pMDI + Nebuhaler (
n = 28). Dose-dependent effects were demonstrated on asthma symptoms (
p = 0.0001), daily peak expiratory flow (
p = 0.02), blood eosinophils (
p = 0.0001), urinary cortisol output per day (
p = 0.0001), serum cortisol (
p = 0.006), serum osteocalcin (
p = 0.0001), and the oropharyngeal
Candida colony count (
p = 0.0007, analysis of covariance). The ratio of the responses to the two inhalation devices approximated 1.0 for each index measured; that is, no significant between-device difference was found (
p ≥ 0.29). However, the 95% confidence limits for the ratio of their respective systemic effects on osteocalcin production were 0.83 to 1.48. Thus in adults who use inhalation devices efficiently and have optimally controlled asthma, conversions from the pMDI + Nebuhaler to the Turbuhaler may reasonably be made at milligram equivalent doses of budesonide, then down-titrated to minimize possible systemic effects. Because earlier studies have shown that the Turbuhaler can double intrapulmonary drug delivery in comparison with a pMDI without a spacer, a 50% dose reduction may be indicated when converting from a pMDI to the Turbuhaler. (J Allergy Clin Immunol 1997;99:186-93.)