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Population pharmacokinetics and pharmacodynamics of inhaled ciclesonide and fluticasone propionate in patients with persistent asthma

Jian Xu, Rüdiger Nave, Gezim Lahu, Eric Derom UGent and Hartmut Derendorf (2010) JOURNAL OF CLINICAL PHARMACOLOGY. 50(10). p.1118-1127
abstract
Inhaled corticosteroids, such as fluticasone propionate (FP) and ciclesonide (CIC), are commonly used for the treatment of asthma. The objectives of this study were to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of FP and a pharmacologically active metabolite of CIC (desisobutyryl-ciclesonide [Des-CIC]) using a nonlinear mixed-effects modeling approach, to investigate selected covariate effects on PK and PD parameters of FP and Des-CIC, and to assess the systemic effects of FP and CIC on serum cortisol suppression in patients with persistent asthma. This was a randomized, double-blind, placebo-controlled, double-dummy, 5-period, crossover, multicenter clinical study. A total of 32 patients were enrolled and given basic asthma medication (salmeterol 50 mu g twice per day [BID] and CIC 160 mu g daily in the evening) through the entire study. During crossover periods, patients were given placebo or CIC 160 mu g BID (ex actuator), CIC 320 mu g BID (ex actuator), FP 220 mu g BID (ex actuator), or FP 440 mu g BID (ex actuator). The FP and Des-CIC PK were described using a 1-compartment and a 2-compartment linear model with first-order absorption process. The FP population PK parameter estimates of the first-order rate constant, relative clearance, and volume of distribution were 4.07 1/h, 890 L/h, and 9800 L, respectively. The Des-CIC PK parameter estimates of the first-order absorption rate constant were 2.63 1/h, clearance 202 L/h (non-CIC treatment) or 271 L/h (CIC treatment), and volume of distribution 947 L. Gender was a significant covariate on the maximum cortisol release rate (male, 3440 mu g/h; female, 4310 mu g/h). The CIC showed the least serum cortisol suppression of the tested dosing regimens.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
inhaled corticosteroids, Population pharmacokinetics and pharmacodynamics, cortisol suppression, ciclesonide, fluticasone propionate, asthma, ADRENAL AXIS FUNCTION, CORTISOL SECRETION, CIRCADIAN-RHYTHM, CORTICOSTEROIDS, SERUM
journal title
JOURNAL OF CLINICAL PHARMACOLOGY
J. Clin. Pharmacol.
volume
50
issue
10
pages
1118 - 1127
Web of Science type
Article
Web of Science id
000281862400003
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
3.59 (2010)
JCR rank
59/249 (2010)
JCR quartile
1 (2010)
ISSN
0091-2700
DOI
10.1177/0091270009354994
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1861291
handle
http://hdl.handle.net/1854/LU-1861291
date created
2011-07-26 16:04:47
date last changed
2016-12-19 15:46:41
@article{1861291,
  abstract     = {Inhaled corticosteroids, such as fluticasone propionate (FP) and ciclesonide (CIC), are commonly used for the treatment of asthma. The objectives of this study were to characterize pharmacokinetics (PK) and pharmacodynamics (PD) of FP and a pharmacologically active metabolite of CIC (desisobutyryl-ciclesonide [Des-CIC]) using a nonlinear mixed-effects modeling approach, to investigate selected covariate effects on PK and PD parameters of FP and Des-CIC, and to assess the systemic effects of FP and CIC on serum cortisol suppression in patients with persistent asthma. This was a randomized, double-blind, placebo-controlled, double-dummy, 5-period, crossover, multicenter clinical study. A total of 32 patients were enrolled and given basic asthma medication (salmeterol 50 mu g twice per day [BID] and CIC 160 mu g daily in the evening) through the entire study. During crossover periods, patients were given placebo or CIC 160 mu g BID (ex actuator), CIC 320 mu g BID (ex actuator), FP 220 mu g BID (ex actuator), or FP 440 mu g BID (ex actuator). The FP and Des-CIC PK were described using a 1-compartment and a 2-compartment linear model with first-order absorption process. The FP population PK parameter estimates of the first-order rate constant, relative clearance, and volume of distribution were 4.07 1/h, 890 L/h, and 9800 L, respectively. The Des-CIC PK parameter estimates of the first-order absorption rate constant were 2.63 1/h, clearance 202 L/h (non-CIC treatment) or 271 L/h (CIC treatment), and volume of distribution 947 L. Gender was a significant covariate on the maximum cortisol release rate (male, 3440 mu g/h; female, 4310 mu g/h). The CIC showed the least serum cortisol suppression of the tested dosing regimens.},
  author       = {Xu, Jian and Nave, R{\"u}diger and Lahu, Gezim and Derom, Eric and Derendorf, Hartmut},
  issn         = {0091-2700},
  journal      = {JOURNAL OF CLINICAL PHARMACOLOGY},
  keyword      = {inhaled corticosteroids,Population pharmacokinetics and pharmacodynamics,cortisol suppression,ciclesonide,fluticasone propionate,asthma,ADRENAL AXIS FUNCTION,CORTISOL SECRETION,CIRCADIAN-RHYTHM,CORTICOSTEROIDS,SERUM},
  language     = {eng},
  number       = {10},
  pages        = {1118--1127},
  title        = {Population pharmacokinetics and pharmacodynamics of inhaled ciclesonide and fluticasone propionate in patients with persistent asthma},
  url          = {http://dx.doi.org/10.1177/0091270009354994},
  volume       = {50},
  year         = {2010},
}

Chicago
Xu, Jian, Rüdiger Nave, Gezim Lahu, Eric Derom, and Hartmut Derendorf. 2010. “Population Pharmacokinetics and Pharmacodynamics of Inhaled Ciclesonide and Fluticasone Propionate in Patients with Persistent Asthma.” Journal of Clinical Pharmacology 50 (10): 1118–1127.
APA
Xu, Jian, Nave, R., Lahu, G., Derom, E., & Derendorf, H. (2010). Population pharmacokinetics and pharmacodynamics of inhaled ciclesonide and fluticasone propionate in patients with persistent asthma. JOURNAL OF CLINICAL PHARMACOLOGY, 50(10), 1118–1127.
Vancouver
1.
Xu J, Nave R, Lahu G, Derom E, Derendorf H. Population pharmacokinetics and pharmacodynamics of inhaled ciclesonide and fluticasone propionate in patients with persistent asthma. JOURNAL OF CLINICAL PHARMACOLOGY. 2010;50(10):1118–27.
MLA
Xu, Jian, Rüdiger Nave, Gezim Lahu, et al. “Population Pharmacokinetics and Pharmacodynamics of Inhaled Ciclesonide and Fluticasone Propionate in Patients with Persistent Asthma.” JOURNAL OF CLINICAL PHARMACOLOGY 50.10 (2010): 1118–1127. Print.