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Population Pharmacokinetics and Pharmacodynamics of Ciclesonide.
- Source :
- Journal of Clinical Pharmacology; Apr2003, Vol. 43 Issue 4, p365-378, 14p
- Publication Year :
- 2003
-
Abstract
- Ciclesonide is a novel glucocorticoid that is converted into ciclesonide-active principle (CIC-AP) in the lung. The study objectives were to identify a structural model for population pharmacokinetic (PK) analysis of CIC-AP using nonlinear mixed-effects modeling, assess the influence of select covariates on PK and/or pharmacodynamic (PD) parameters, and investigate the effects of CIC-AP on endogenous cortisol. Pooled concentration data from nine phase I studies (dose: 400-3600 μg) involving healthy and asthmatic patients were included in the PK analysis. There were 151 subjects (3300 observations) for the CIC-AP population PK analysis. Various models examined inter- and intrasubject variability for the PK parameters. Population estimates of the PK parameters of clearance and volume of distribution were 396 L/h (64.8% coefficient of variation [CV]) and 1190 L (41.2% CV), respectively. Pharmacodynamic population estimates included maximum cortisol release rate, 3140 ng/h (5.4% CV). The EC<subscript>50</subscript> of CIC-AP was 0.88 ng/mL. Ciclesonide is a safe corticosteroid that causes negligible cortisol suppression. The disposition and effect of CIC-AP can be described using mixed-effect modeling. The estimated EC<subscript>50</subscript> is similar to mean C<subscript>max</subscript> from an 800-μg dose, further suggesting CIC-AP has little effect on cortisol suppression. [ABSTRACT FROM AUTHOR]
- Subjects :
- GLUCOCORTICOIDS
HYDROCORTISONE
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00912700
- Volume :
- 43
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 10476317