Asthma
Conditions
Keywords
Albuterol, Forced expiratory volume in one second, Dose at fifty percent of maximum effect, Maximum effective dose, Metered dose inhaler, Nebulizer
Brief summary
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
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.
Interventions
DRUGalbuterol
Albuterol administered sequentially 180mcg (MDI), 90mcg (MDI), 90mcg(MDI), 90mcg (MDI), 90mcg (MDI), 2.5mg (nebulized)
Sponsors
Nemours Children's Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effective Dose 50% (ED50) | 15 minutes after each dose | ED50 is the cumulative dose of albuterol required to bring about 50% of maximum effect of albuterol |
| Effect Maximum (Emax) | 15 minutes after each dose | Maximum percentage of predicted FEV1 effect |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from our asthma research clinic database or newspaper advertisements. Participants were recruited from 07/1993 to 10/1994.
Pre-assignment details
Participants had to withhold inhaled short-acting beta2 agonist or inhaled anticholinergic drugs for 8 h, oral antihistamines for 5 days, theophylline for 24 h, and cromolyn, nedocromil, and inhaled corticosteroids for 2 h prior to the study.
Participants by arm
| Arm | Count |
|---|---|
| Albuterol Increasing doses of albuterol by MDI and nebulizer solution | 81 |
| Total | 81 |
Baseline characteristics
| Characteristic | Albuterol |
|---|---|
| Age, Categorical <=18 years | 31 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants |
| Age, Continuous | 30.2 years STANDARD_DEVIATION 17.4 |
| Region of Enrollment United States | 81 participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 81 |
| serious Total, serious adverse events | 0 / 81 |
Outcome results
Primary
Effective Dose 50% (ED50)
ED50 is the cumulative dose of albuterol required to bring about 50% of maximum effect of albuterol
Time frame: 15 minutes after each dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albuterol | Effective Dose 50% (ED50) | 141 ug |
Primary
Effect Maximum (Emax)
Maximum percentage of predicted FEV1 effect
Time frame: 15 minutes after each dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albuterol | Effect Maximum (Emax) | 24.0 percentage of predicted |