吸入用倍氯米松/福莫特罗干粉吸入剂的全身暴露量取决于年龄和体型。
Systemic exposure to inhaled beclometasone/formoterol DPI is age and body size dependent.
作者信息
Chawes B L, Govoni M, Kreiner-Møller E, Vissing N H, Poorisrisak P, Mortensen L, Nilsson E, Bisgaard A, Dossing A, Deleuran M, Skytt N L, Samandari N, Piccinno A, Sergio F, Ciurlia G, Poli G, Acerbi D, Singh D, Bisgaard H
机构信息
Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
Department of Clinical Pharmacology, Chiesi Farmaceutici S.p.A., Parma, Italy.
出版信息
Respir Med. 2014 Aug;108(8):1108-16. doi: 10.1016/j.rmed.2014.05.007. Epub 2014 Jun 17.
AIM
Prescription of inhaled corticosteroids to children with asthma is recommended at half the nominal dose of adults in order to reduce the risk of systemic side effects. However, there is a lack of pharmacokinetic trials supporting such dose reduction regimens. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed dose combination of beclometasone-dipropionate (BDP) and formoterol after dry powder inhaler (DPI) administration in children, adolescents and adults.
METHODS
The pharmacokinetic profiles of formoterol and beclometasone-17-monopropionate (B17MP; active metabolite of BDP) were evaluated over 8 h from two independent studies comprising children (6-11yrs, n = 27), adolescents (12-17 yrs, n = 28) and adults (≥18 yrs, n = 30) receiving a single, fixed dose of BDP/formoterol (children: 200 μg/24 μg, adolescents and adults: 400 μg/24 μg) via DPI.
RESULTS
The systemic exposure (AUC) for children versus adults was almost doubled for formoterol and similar for B17MP despite the halved BDP dose administered in children. In adolescents the AUC for formoterol and B17MP were approximately one third higher than in adults for both compounds. Upon normalization for the BDP/formoterol dose in the three populations the AUC and peak concentration (C(max)) correlated inversely with age and body surface area of the patients (r ≤ -0.53; p < 0.0001).
CONCLUSION
The systemic exposure to the active ingredients of BDP/formoterol administered as DPI correlates inversely with age and body size suggesting that dry powder dosage regimens should be adjusted for age and body size to avoid high systemic drug levels in children.
目的
为降低全身副作用风险，建议给哮喘儿童使用的吸入性糖皮质激素剂量为成人标称剂量的一半。然而，缺乏支持这种剂量减少方案的药代动力学试验。因此，我们旨在比较儿童、青少年和成人使用干粉吸入器（DPI）吸入丙酸倍氯米松（BDP）和福莫特罗固定剂量组合后活性成分的全身暴露情况。
方法
通过两项独立研究评估福莫特罗和倍氯米松 - 17 - 单丙酸酯（B17MP；BDP的活性代谢物）的药代动力学特征，这两项研究包括接受单次固定剂量BDP/福莫特罗（儿童：200μg/24μg，青少年和成人：400μg/24μg）的儿童（6 - 11岁，n = 27）、青少年（12 - 17岁，n = 28）和成人（≥18岁，n = 30），给药时间为8小时。
结果
尽管儿童使用的BDP剂量减半，但儿童与成人相比，福莫特罗的全身暴露（AUC）几乎增加了一倍，B17MP的全身暴露相似。在青少年中，两种化合物的福莫特罗和B17MP的AUC均比成人高约三分之一。对三个群体中的BDP/福莫特罗剂量进行标准化后，AUC和峰浓度（C(max)）与患者的年龄和体表面积呈负相关（r≤ - 0.53；p < 0.0001）。
结论
以DPI形式给药的BDP/福莫特罗活性成分的全身暴露与年龄和体型呈负相关，这表明应根据年龄和体型调整干粉给药方案，以避免儿童体内药物全身水平过高。
Zotero 插件