Dose-response of Albuterol in Asthmatics

Study Overview
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Brief Summary
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The purpose of this study was to determine the lung function response after increasing doses of albuterol (a bronchodilator) in children and adults with asthma.

Detailed Description
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Inhaled short-acting b2-agonists (SABA) are the most potent bronchodilators used today to treat acute symptoms of asthma and albuterol, a partial b2-agonist, is the most frequently prescribed asthma medication in the US. Although universally used in for acute asthma symptoms, SABA have been associated with a significant degree of interpatient variability. Many studies have characterized the SABA dose to bronchodilator response relationship under controlled conditions. However, few studies have explored the magnitude and sources of bronchodilator response variability, and no studies have characterized the dose versus bronchodilator response relationship using population pharmacokinetic/pharmacodynamic (PPK/PD) modeling. In the present study, we characterized the relationship between inhaled doses of albuterol and bronchodilation in 81 children and adults with moderate to severe persistent asthma using a population pharmacodynamic approach. The purpose of this study was to obtain estimates of the pharmacodynamic parameters that characterize the dose-response curve, including maximal dose for bronchodilation, and to quantify and identify sources of interpatient pharmacodynamic variability.

Official Title
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Exclusion of Asthmatics From Clinical Trials Due to the 15 Percent Rule

Conditions
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Asthma

Intervention / Treatment
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* Drug: albuterol


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria: Well-defined history of physician diagnosed asthma Any ethnic background 8 to 65 years old Baseline pre-bronchodilator FEV1 of 40% to 80% predicted for age, height, and gender No oral corticosteroid use, emergency room visits, or hospitalizations within the previous 3 months Nonsmokers or less than a 5 pack-year history with no smoking in the previous year Normal physical exam and no confounding diseases were selected Able to withhold inhaled short-acting b2-agonists or inhaled anticholinergic drugs for 8 hours, oral antihistamines for 5 days, theophylline for 24 hours, and cromolyn, nedocromil, and inhaled corticosteroids for 2 hours prior to the study.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: albuterol|Albuterol administered sequentially 180mcg (MDI), 90mcg (MDI), 90mcg(MDI), 90mcg (MDI), 90mcg (MDI), 2.5mg (nebulized)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective Dose 50% (ED50) | ED50 is the cumulative dose of albuterol required to bring about 50% of maximum effect of albuterol | 15 minutes after each dose | 
| Effect Maximum (Emax) | Maximum percentage of predicted FEV1 effect | 15 minutes after each dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Albuterol, Forced expiratory volume in one second, Dose at fifty percent of maximum effect, Maximum effective dose, Metered dose inhaler, Nebulizer