Konstantina Soulele, Panos Macheras, Vangelis Karalis
Laboratory of Biopharmaceutics-Pharmacokinetics, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece
Objectives: To use population pharmacokinetic modeling in order to describe the concentration-time data of fluticasone and salmeterol obtained from administration of two different dry powder inhalers: the traditional multi-dose and a novel single-dose device.
Methods: Plasma concentration – time data were obtained from a single dose 2×2 bioequivalence study comparing the two dry powder inhalers in 60 healthy male and subjects under fasting conditions. Concentration – time data of fluticasone and salmeterol were fitted to one- and two-compartment pharmacokinetic models assuming first order absorption and elimination kinetics. Elimination was considered to take place in the central compartment. Two different residual error models were tested: a proportional and an exponential error model. Demographic data like age, gender, body weight, height, and body mass index were used as covariates. The non-linear mixed effect models were applied separately to each drug (i.e. fluticasone or salmeterol) and type of inhaler. The entire work was implemented in Monolix v.4.2.
Results: For the one-compartment model, the population pharmacokinetic parameters of first-order rate constant and, the normalized with fraction of dose absorbed, volume of distribution and clearance were estimated. In case of the two-compartment model, the volume of distribution of the second compartment, as well as the first order transfer rate constants between the central and the peripheral compartment were additionally calculated. The estimates obtained from the two different dry powder inhalers were similar to each other. Significant covariates were also detected. The results found in this work were in accordance with previous studies describing the pharmacokinetics of an inhaled fluticasone multi-dose product in patients [1].
Conclusions: The utilized population pharmacokinetic models successfully described the concentration-time profile of fluticasone / salmeterol. Similar estimates were found for the two dry powder inhalers.
References:
[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. J Clin Pharmacol (2010) 50(10): 1118-27.
Reference: PAGE 23 (2014) Abstr 3110 [www.page-meeting.org/?abstract=3110]
Poster: Drug/Disease modeling - Infection