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Dose‐response of inhaled diltiazem on airway reactivity to methacholine and exercise in subjects with mild asthma
Author(s) -
Hendeles Leslie,
Hill Malcolm,
Harman Eloise,
Moore Peter,
Pieper John
Publication year - 1988
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1988.48
Subject(s) - methacholine , medicine , asthma , diltiazem , airway , anesthesia , cardiology , respiratory disease , lung , calcium
Methacholine challenges were performed by 10 asthmatic subjects, 2 hours before and 15 minutes after placebo (diluent alone) and 5, 10, 15, 30, and 60 mg inhaled diltiazem given in a single‐blind crossover manner. There was no significant change from placebo in the dose of methacholine required to produce a 20% decrease in forced expiratory volume in the first second (FEV 1 ) (PD 20 ); the fold increase in PD 20 from baseline was 1.1 ± 0.1 after placebo, 1.4 ± 0.2 after 5 mg, 1.8 ± 0.3 after 10 mg, 1.4 ± 0.2 after 15 mg, 1.6 ± 0.2 after 30 mg, and 1.2 ± 0.1 after 60 mg. There was a 1% chance that we missed a twofold difference between placebo and the 10 mg dose because of inadequate sample size. Fifteen minutes before a standardized exercise challenge, 10 subjects received placebo, 10 mg, and the highest dose tolerated during the methacholine study (20 to 45 mg) in a randomized double‐blind crossover design. The mean ± SE maximum postexercise decrease in FEV 1 was 28.8% ± 5.7% after placebo, 23.4% ± 4.6% after 10 mg, and 20.8% ± 3.0% after high‐dose diltiazem (P > 0.05). There was a 12% chance that we missed a 15% difference between placebo and the high‐dose regimen because of inadequate sample size. We conclude that diltiazem does not attenuate airway reactivity to methacholine or exercise even when high concentrations are delivered to the lungs. Clinical Pharmacology and Therapeutics (1988) 43, 387–392; doi: 10.1038/clpt.1988.48