title: Bioavailability of inhaled fluticasone propionate via chambers/masks in young children.
abstract: We determined lung bioavailability of a fluticasone propionate (FP) pressurised metred-dose inhaler (Flovent HFA; GlaxoSmithKline, Research Triangle Park, NC, USA) administered via AeroChamber Plus (Monaghan Medical, Plattsburgh, NY, USA) with Facemask and Babyhaler (GlaxoSmithKline) valved holding chambers (VHCs) using a population pharmacokinetic approach. Children from 1 to <4 yrs of age with stable asthma but a clinical need for inhaled corticosteroid therapy were administered 88 μg FP hydrofluoroalkane (2 × 44 μg) twice daily delivered through the two devices in an open-label, randomised crossover manner for 8 days each. Patients were randomised to one of three sparse sampling schedules for blood collection throughout the 12-h dosing interval on the 8th day of each treatment for pharmacokinetic analysis. The area under the FP plasma concentration-time curve (AUC) was determined for each regimen. 17 children completed the study. The population mean AUC following FP with AeroChamber Plus with Facemask was 97.45 pg·h·mL(-1) (95% CI 85.49-113.32 pg·h·mL(-1)) and with Babyhaler was 51.55 pg·h·mL(-1) (95% CI 34.45-64.46 pg·h·mL(-1)). The relative bioavailability (Babyhaler/AeroChamber Plus) was 0.53 (95% CI 0.30-0.75). Clinically significant differences in lung bioavailability were observed between the devices. VHCs are not interchangeable, as differences in drug delivery to the lung may occur. A population pharmacokinetic approach can be used to determine lung bioavailability of FP.
authors.affiliation: Center for Pharmacogenomics and Translational Research, Dept of Biomedical Research, Nemours Children's Clinic, Jacksonville, FL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Blake
authors.forename: R
authors.initials: R
authors.lastname: Mehta
authors.forename: T
authors.initials: T
authors.lastname: Spencer
authors.forename: R L
authors.initials: RL
authors.lastname: Kunka
authors.forename: L
authors.initials: L
authors.lastname: Hendeles
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000730:Androstadienes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy*; D001682:Biological Availability; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002675:Child, Preschool; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004867:Equipment Design; D005260:Female; D000068298:Fluticasone; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D008168:Lung / Q000187:drug effects; D008297:Male; D009330:Nebulizers and Vaporizers
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D001993:Bronchodilator Agents; D000068298:Fluticasone