Allergen challenge and deposition of nedocromil sodium in asthma.
We examined whether the acute protective effect of nedocromil sodium aerosol could be enhanced by increasing the deposition uniformity of the drug in the lungs of adult patients with allergic asthma. Ten patients with mild-to-moderate asthma were challenged with the same doses of allergen on two occasions in a randomized manner. Thirty minutes before these challenges, patients inhaled 4 mg nedocromil sodium, admixed with the radioisotope (99m)technetium. Radiolabeled drug was inhaled during slow (25.4 +/- 4.6 L/min) and faster (58.0 +/- 7.3 L/min) inhalations from a 700 ml holding chamber. Percent changes in FEV(1) at the same top dose of allergen on the two treatment visits were compared. Lung deposition fraction (LDF) and indices of distribution uniformity, quantified from gamma camera images, were also compared. Acute protection against allergen challenge was similar and complete after slow or faster inspiration of nedocromil sodium. Mean (+/- SD) allergen-induced changes in FEV(1) were -1.05 +/- 2.78% and -0.39 +/- 2.80%, respectively, compared to -26.30 +/- 8.49% on a screening challenge (no drug). Mean LDF was also similar on the two visits, averaging 16.4 +/- 4.6% and 16.1 +/- 7.2% of administered drug, respectively. Distribution of nedocromil sodium was most uniform after slow inspiration, but increased uniformity was not related to enhanced protection. Complete protection against acute bronchoconstriction induced by inhaled allergen can be obtained with 4 mg of nedocromil sodium aerosol, inhaled from a large volume holding chamber, 30 min before the exposure, and at inspiratory flow rates between approximately 20-60 L/min. Protection does not appear to be enhanced by increased uniformity of drug distribution within the lungs.
Laube
Beth L
BL
Johns Hopkins University of Medical Institutions, Baltimore, Maryland 21287-2533, USA. blaube@jhmi.edu
Lin
Ta-Chun
TC
Valleteau
Anne
A
Dalby
Richard N
RN
Diemer
Fiona B
FB
Togias
Alkis G
AG
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage / Q000493:pharmacokinetics; D000485:Allergens / Q000276:immunology*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015902:Gamma Cameras; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers; D017835:Nedocromil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric
D000336:Aerosols; D000485:Allergens; D018927:Anti-Asthmatic Agents; D017835:Nedocromil