{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T08:40:59Z","timestamp":1761986459579,"version":"build-2065373602"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":250,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:p><jats:bold>Study Objective.<\/jats:bold> To determine whether the methacholine challenge method used for albuterol can be applied to assess long\u2010acting \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic agonist (LABA) bioequivalence, which would require a sufficiently steep dose\u2010response curve.<\/jats:p><jats:p><jats:bold>Design.<\/jats:bold> Prospective, unblinded, randomized, 2\u2013way crossover study.<\/jats:p><jats:p><jats:bold>Setting.<\/jats:bold> University medical center clinical research laboratory.<\/jats:p><jats:p><jats:bold>Patients.<\/jats:bold> Ten adults, aged 21\u201358 years, with mild asthma (forced expiratory volume in 1 sec [FEV<jats:sub>1<\/jats:sub>] \u2265 70% predicted) and a baseline provocational concentration of methacholine required to decrease FEV<jats:sub>1<\/jats:sub> by 20% (PC<jats:sub>20<\/jats:sub>) of 4 mg\/ml or less completed the study.<\/jats:p><jats:p><jats:bold>Intervention.<\/jats:bold> Patients were randomized to receive a single dose of either 12 or 24 \u03bcg of formoterol delivered by a dry powder inhaler; 3\u20137 days later, at the same time of day, they received the other dose.<\/jats:p><jats:p><jats:bold>Measurements and Main Results.<\/jats:bold> The FEV<jats:sub>1<\/jats:sub> was measured before and 1 hour after dosing, followed by performance of a methacholine challenge. Statistical analysis was performed by the 2\u2013sample regression method for crossover studies. The dose\u2010response curve for bronchodilatation was flat; the mean \u00b1 SD increase in FEV<jats:sub>1<\/jats:sub> after formoterol 12 and 24 \u03bcg was 14 \u00b1 5% and 14 \u00b1 8%, respectively (p&gt;0.05). In contrast, the geometric mean PC<jats:sub>20<\/jats:sub> (95% confidence interval) was 7 mg\/ml (2\u201322 mg\/ml) after the 12\u2010\u03bcg dose and 16 mg\/ml (5\u201345 mg\/ml) after the 24\u2010\u03bcg dose (p &lt; 0.001).<\/jats:p><jats:p><jats:bold>Conclusion.<\/jats:bold> Bioassay by methacholine challenge will be useful for bioequivalence studies of LABAs. A sample of at least 28 patients will be required for formoterol when methacholine challenge is performed in an optimal manner. The sample size may differ for other LABAs.<\/jats:p>","DOI":"10.1592\/phco.31.5.449","type":"journal-article","created":{"date-parts":[[2011,4,25]],"date-time":"2011-04-25T13:56:27Z","timestamp":1303739787000},"page":"449-457","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Methacholine Challenge as a Clinical Bioassay of Pulmonary Delivery of a Long\u2010Acting \u03b2<sub>2<\/sub>\u2010Adrenergic Agonist"],"prefix":"10.1002","volume":"31","author":[{"given":"Sreekala","family":"Prabhakaran","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Shuster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Ahrens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Hendeles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"e_1_2_1_2_2","unstructured":"National Heart Lung and Blood Institute.National asthma education and prevention program. 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