Population pharmacokinetics and pharmacodynamics of inhaled ciclesonide and
fluticasone propionate in patients with persistent asthma.
Author(s): Xu J, Nave R, Lahu G, Derom E, Derendorf H.
Affiliation(s): Department of Pharmaceutics, College of Pharmacy, University of Florida,
Gainesville, FL 32610, USA.
Publication date & source: 2010, J Clin Pharmacol. , 50(10):1118-27
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 µg twice per day [BID] and CIC 160 µg daily in the evening)
through the entire study. During crossover periods, patients were given placebo
or CIC 160 µg BID (ex actuator), CIC 320 µg BID (ex actuator), FP 220 µg BID (ex
actuator), or FP 440 µg 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
µg/h; female, 4310 µg/h). The CIC showed the least serum cortisol suppression of
the tested dosing regimens.
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