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Single‐Dose Pharmacokinetics of Roflumilast in Children and Adolescents
Author(s) -
Neville Kathleen A.,
Szefler Stanley J.,
AbdelRahman Susan M.,
Lahu Gezim,
Zech Karl,
Herzog Rolf,
Bethke Thomas D.,
Gleason Melanie C.,
Kearns Gregory L.
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008319466
Subject(s) - roflumilast , pharmacokinetics , crossover study , medicine , bioequivalence , pharmacology , asthma , cohort , alternative medicine , pathology , copd , placebo
Roflumilast is an orally administered phosphodiesterase 4 inhibitor that has potential for use in pediatric patients with asthma. The pharmacokinetics of roflumilast and roflumilast N‐oxide were examined in adolescents and children with stable mild to moderate asthma in an open‐label crossover study with age‐stratification and 2 treatment periods (100‐μg dose in period 1, 250‐μg dose in period 2) separated by a washout period. Plasma concentrations were measured by high‐performance liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were determined using standard noncompartmental methods and compared between study groups and within the entire cohort. Roflumilast was well tolerated. Linear relationships were evident for dose and area under the plasma drug concentration‐time curve extrapolated to infinity for both roflumilast ( r 2 = 0.36, P < .01) and roflumilast N‐oxide ( r 2 = 0.39, P < .01). With the exception of dose‐normalized maximum plasma concentration (mean 1.1 and 0.8 μg/L per 1 μg/kg dose for adolescents and children, respectively), pharmacokinetic parameters for roflumilast and roflumilast N‐oxide were not different between age groups and were similar to adults.