Kathryn Blake1, Rajanikanth Madabushi2, Hartmut Derendorf2, John Lima3. 1. Center for Clinical Pediatric Pharmacology Research, Nemours Children's Clinic, Jacksonville, FL. Electronic address: kblake@nemours.org. 2. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL. 3. Center for Clinical Pediatric Pharmacology Research, Nemours Children's Clinic, Jacksonville, FL.
Abstract
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 microg of albuterol from a metered-dose inhaler (MDI), and then 90 microg every 15 min until maximum improvement or 540 microg 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 microg, 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 > or = 200 mL in 21% of participants. Heart rate and BP were unchanged from baseline after maximal albuterol doses. CONCLUSIONS: Our model predicts that 180 microg 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.
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 microg of albuterol from a metered-dose inhaler (MDI), and then 90 microg every 15 min until maximum improvement or 540 microg 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 microg, 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 > or = 200 mL in 21% of participants. Heart rate and BP were unchanged from baseline after maximal albuterol doses. CONCLUSIONS: Our model predicts that 180 microg 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.
Authors: Katherine A Drake; Dara G Torgerson; Christopher R Gignoux; Joshua M Galanter; Lindsey A Roth; Scott Huntsman; Celeste Eng; Sam S Oh; Sook Wah Yee; Lawrence Lin; Carlos D Bustamante; Andrés Moreno-Estrada; Karla Sandoval; Adam Davis; Luisa N Borrell; Harold J Farber; Rajesh Kumar; Pedro C Avila; Emerita Brigino-Buenaventura; Rocio Chapela; Jean G Ford; Michael A Lenoir; Fred Lurmann; Kelley Meade; Denise Serebrisky; Shannon Thyne; William Rodríguez-Cintrón; Saunak Sen; José R Rodríguez-Santana; Ryan D Hernandez; Kathleen M Giacomini; Esteban G Burchard Journal: J Allergy Clin Immunol Date: 2013-08-29 Impact factor: 10.793
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