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Original Research: ASTHMA |

Population Pharmacodynamic Model of Bronchodilator Response to Inhaled Albuterol in Children and Adults With Asthma

Kathryn Blake, PharmD; Rajanikanth Madabushi, PhD; Hartmut Derendorf, PhD; John Lima, PharmD
Author and Funding Information

*From the Center for Clinical Pediatric Pharmacology Research (Drs. Blake and Lima), Nemours Children's Clinic, Jacksonville; and Department of Pharmaceutics (Drs. Madabushi and Derendorf), College of Pharmacy, University of Florida, Gainesville, FL.

Correspondence to: Kathryn Blake, PharmD, Center for Clinical Pediatric Pharmacology Research, Nemours Children's Clinic, 807 Childrens Way, Jacksonville, FL 32207; e-mail: kblake@nemours.org


All work was performed in the Center for Clinical Pediatric Pharmacology Research, Nemours Children's Clinic, Jacksonville, FL.

The authors have no conflicts of interest to report.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2008;134(5):981-989. doi:10.1378/chest.07-2991
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Background:  Because interpatient variability in bronchodilation from inhaled albuterol is large and clinically important, we characterized the albuterol dose/response relationship by pharmacodynamic modeling and quantified variability.

Methods:  Eighty-one patients with asthma (24% African American [AA]; 8 to 65 years old; baseline FEV1, 40 to 80% of predicted) received 180 μg of albuterol from a metered-dose inhaler (MDI), and then 90 μg every 15 min until maximum improvement or 540 μg was administered; all then received 2.5 mg of nebulized albuterol. FEV1 was measured 15 min after each dose. The population cumulative dose/response data were fitted with a sigmoid maximum effect of albuterol (Emax) [maximum percentage of predicted FEV1 effect] model by nonlinear mixed-effects modeling. The influence of covariates on maximum percentage of predicted FEV1 reached after albuterol administration (Rmax) and cumulative dose of albuterol required to bring about 50% of maximum effect of albuterol (ED50) and differences between AA and white patients were explored.

Results:  ED50 was 141 μg, and Emax was 24.0%. Coefficients of variation for ED50 and Emax were 40% and 56%, respectively. Ethnicity was a statistically significant covariate (p < 0.05). AA and white patients reached 82.4% and 91.9% of predicted FEV1, respectively (p = 0.0004); and absolute improvement in percentage of predicted FEV1 was 16.6% in AA patients vs 26.7% in white patients (p < 0.0003). There were no baseline characteristic differences between AA and white patients. Nebulized albuterol increased FEV1 ≥ 200 mL in 21% of participants. Heart rate and BP were unchanged from baseline after maximal albuterol doses.

Conclusions:  Our model predicts that 180 μg of albuterol by MDI produces a 14.4% increase in percentage of predicted FEV1 over baseline (11.7% in AA patients, and 17.5% in white patients). Emax varies widely between asthmatic patients. AA patients are less responsive to maximal doses of inhaled albuterol than white patients.

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