Agertoft Lone, Pedersen Soren
Department of Paediatrics, Kolding Hospital, Kolding, Denmark.
Am J Respir Crit Care Med. 2003 Oct 1;168(7):779-82. doi: 10.1164/rccm.200302-200OC. Epub 2003 Jul 31.
Pharmacokinetic studies can be used to measure lung dose of inhaled drugs. The aim of this study was to compare the lung deposition of budesonide (BUD) inhaled from Turbuhaler (AstraZeneca, Lund, Sweden) and fluticasone propionate (FP) inhaled from Diskus (GlaxoSmithKline, London, UK) and to assess if the study design used for pharmacokinetic studies can be simplified. Plasma levels of BUD and FP were measured for 21 hours on five separate days in 15 patients aged 8 to 14 years: (1) Intravenous infusion of 200 microg BUD, (2) intravenous infusion of 200 microg fluticasone dipropionate, (3) inhalation of 800 microg BUD via Turbuhaler, (4) inhalation of 750 microg FP via Diskus, and (5) inhalation of BUD and FP on the same day. Charcoal was ingested to eliminate drug uptake from the gastrointestinal tract. The mean lung deposition of drug after Turbuhaler and Diskus inhalation was 30.8 and 8.0% when BUD and fluticasone were administered on separate days and 29.5% (BUD) and 7.6% (fluticasone) when the two drugs were inhaled on the same day. Lung deposition is four times higher in children after inhalation from Turbuhaler than after inhalation from Diskus. Pharmacokinetic studies with BUD and FP can be simplified because the two treatments can be administered on the same day.
药代动力学研究可用于测量吸入药物的肺部剂量。本研究的目的是比较从都保(阿斯利康,瑞典隆德)吸入的布地奈德(BUD)和从准纳器(葛兰素史克,英国伦敦)吸入的丙酸氟替卡松(FP)的肺部沉积情况,并评估用于药代动力学研究的设计是否可以简化。在15名8至14岁的患者中,于五个不同日期测量了21小时的BUD和FP血浆水平:(1)静脉输注200微克BUD,(2)静脉输注200微克二丙酸氟替卡松,(3)通过都保吸入800微克BUD,(4)通过准纳器吸入750微克FP,以及(5)同一天吸入BUD和FP。摄入活性炭以消除胃肠道对药物的摄取。当BUD和氟替卡松分开给药时,都保和准纳器吸入后药物的平均肺部沉积率分别为30.8%和8.0%,而当两种药物同一天吸入时,分别为29.5%(BUD)和7.6%(氟替卡松)。儿童从都保吸入后的肺部沉积率比从准纳器吸入后高四倍。BUD和FP的药代动力学研究可以简化,因为两种治疗可以在同一天进行。