caa a22 4500 605533989 CHVBK 20210128100840.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s10928-015-9420-6 doi (NATIONALLICENCE)springer-10.1007/s10928-015-9420-6 Quantitative characterization of circadian rhythm of pulmonary function in asthmatic patients treated with inhaled corticosteroids [Elektronische Daten] [Di Zhou, Hongshan Li, Yaning Wang, Guenther Hochhaus, Vikram Sinha, Liang Zhao] The aim of this study was to characterize the circadian rhythm observed for forced expiratory volume in 1s (FEV1) in patients with persistent asthma being treated with inhaled corticosteroids. The database included 3379 FEV1 measurements from 189 patients with mild to moderate asthma. A model using the sum of two Sine functions with periods of 12 and 24h and a constant component of mean circadian rhythm adequately described the circadian rhythm in FEV1 measurements over time. The model adequateness was evaluated by various approaches including visual predictive check (VPC), prediction-corrected VPC, standardized VPC and normalized prediction distribution error. Covariates tested included age, body weight, height, body mass index, baseline FEV1, and sex. Age and height were found to have significant effects on the mean FEV1 level and no covariate was found to have an effect on the magnitude and timing of circadian rhythm. The model predicted that a minimum FEV1 occurred in the early morning and maximum FEV1 occurred in the early afternoon, with a population mean fluctuation of 170mL, which is consistent with the finding that asthma symptoms usually exacerbate in the early morning for patients with persistent asthma. This developed model provides the first quantitative approach to describing FEV1 circadian rhythm with ICS background treatment and provided insight in designing future registration trials for asthma drug development. Springer Science+Business Media New York (outside the USA), 2015 Circadian rhythm nationallicence Asthma nationallicence FEV1 nationallicence Pharmacodynamic model nationallicence Drug development nationallicence Zhou Di Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL, USA aut Li Hongshan Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA aut Wang Yaning Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA aut Hochhaus Guenther Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL, USA aut Sinha Vikram Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA aut Zhao Liang Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/4(2015-08-01), 391-399 1567-567X 42:4<391 2015 42 10928 https://doi.org/10.1007/s10928-015-9420-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-015-9420-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhou Di Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL, USA aut NATIONALLICENCE 700 1- Li Hongshan Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA aut NATIONALLICENCE 700 1- Wang Yaning Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA aut NATIONALLICENCE 700 1- Hochhaus Guenther Department of Pharmaceutics, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL, USA aut NATIONALLICENCE 700 1- Sinha Vikram Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA aut NATIONALLICENCE 700 1- Zhao Liang Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/4(2015-08-01), 391-399 1567-567X 42:4<391 2015 42 10928