Single-dose pharmacokinetics of roflumilast in children and adolescents.
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-microg dose in period 1, 250-microg 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 microg/L per 1 microg/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.
Department of Pediatrics, University of Missouri-Kansas City and the Children's Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64079, USA.
Kathleen A
KA
Neville
Stanley J
SJ
Szefler
Susan M
SM
Abdel-Rahman
Gezim
G
Lahu
Karl
K
Zech
Rolf
R
Herzog
Thomas D
TD
Bethke
Melanie C
MC
Gleason
Gregory L
GL
Kearns
D000293:Adolescent; D000631:Aminopyridines / Q000009:adverse effects / Q000493:pharmacokinetics*; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001549:Benzamides / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003521:Cyclopropanes / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry
D000631:Aminopyridines; D018927:Anti-Asthmatic Agents; D001549:Benzamides; D003521:Cyclopropanes; D010726:Phosphodiesterase Inhibitors; C424423:Roflumilast