Allergen challenge and deposition of nedocromil sodium in asthma

Beth L. Laube, Ta Chun Lin, Anne Valleteau, Richard N. Dalby, Fiona B. Diemer, Alkis G. Togias

Research output: Contribution to journalArticlepeer-review

Abstract

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 99mtechnetium. 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 FEV1 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 FEV1 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 ∼20-60 L/min. Protection does not appear to be enhanced by increased uniformity of drug distribution within the lungs.

Original languageEnglish (US)
Pages (from-to)415-425
Number of pages11
JournalJournal of Aerosol Medicine: Deposition, Clearance, and Effects in the Lung
Volume15
Issue number4
DOIs
StatePublished - Dec 1 2002

Keywords

  • Acute antigen response
  • Aerosol deposition
  • Asthma
  • Nedocromil sodium

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology (medical)

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