Center for Pharmacogenomics and Translational Research, Dept of Biomedical Research, Nemours Children's Clinic, Jacksonville, FL, USA.
Eur Respir J. 2012 Jan;39(1):97-103. doi: 10.1183/09031936.00185510. Epub 2011 Sep 20.
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.
我们采用群体药代动力学方法,研究了经 AeroChamber Plus (美国北卡罗来纳州三角研究园的 Monaghan Medical 公司生产)带面罩和 Babyhaler (美国北卡罗来纳州三角研究园的 GlaxoSmithKline 公司生产)活瓣储雾罐给药的丙酸氟替卡松(FP)计量吸入器(Flovent HFA;GlaxoSmithKline)的肺部生物利用度。1 至<4 岁的哮喘稳定但临床需要吸入皮质激素治疗的患儿,以开放、随机交叉方式,每天两次接受两种装置各 88 μg FP 氢氟烷(2×44 μg)治疗,共 8 天。第 8 天治疗期间,患者按三种稀疏采样方案中的一种,在 12 小时给药间隔内采集血样,用于药代动力学分析。确定了每个方案下 FP 的血浆浓度-时间曲线下面积(AUC)。17 名患儿完成了研究。经 AeroChamber Plus 带面罩和 Babyhaler 给药后,FP 的群体平均 AUC 分别为 97.45 pg·h·mL(-1)(95%CI 85.49-113.32 pg·h·mL(-1))和 51.55 pg·h·mL(-1)(95%CI 34.45-64.46 pg·h·mL(-1))。(Babyhaler/AeroChamber Plus)相对生物利用度为 0.53(95%CI 0.30-0.75)。两种装置之间观察到肺部生物利用度的临床显著差异。VHC 不可互换,因为药物向肺部的输送可能存在差异。群体药代动力学方法可用于确定 FP 的肺部生物利用度。