Gupta Samir K, Kantesaria Bhavna, Banfield Christopher, Wang Zaiqi
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Br J Clin Pharmacol. 2007 Aug;64(2):174-84. doi: 10.1111/j.1365-2125.2007.02859.x. Epub 2007 Feb 23.
The aim of this study was to identify the dose of desloratadine in children aged > or =6 months- < or =2 years that would yield a single-dose target exposure (AUC) comparable with that in adults taking 5 mg desloratadine as syrup.
In a phase 1, single-dose, open-label, pharmacokinetic study in 58 children aged > or =6 months- <1 year and > or =1 year- < or =2 years were randomly assigned to desloratadine syrup 0.625 mg (1.25 ml) and 1.25 mg (2.5 ml), respectively. Because the volume of blood that could be collected from individual subjects was limited, a population pharmacokinetic approach was used to estimate the pharmacokinetics of desloratadine. Safety was assessed based on results of screening and postdose physical examinations, laboratory safety tests, vital signs, and adverse events.
The apparent clearance (CL/F) of desloratadine, population estimate (%CV), in children aged > or =6 months- <1 year was 27.8 l h(-1) (35) and corresponding values in children > or =1 year- < or =2 years was 35.5 l h(-1) (51), compared with 137 l h(-1) (58) for adults. The CL/F ratios (children to adults) indicated that doses of 1 mg for > or =6 months- <1 year and 1.25 mg for > or =1 year- < or =2 years would result in similar systemic exposure to that observed in adults receiving the recommended 5 mg dose. Desloratadine was well tolerated with no safety issues.
Doses of 1.0 and 1.25 mg in children aged > or =6 months- < or =2 years should result in an exposure to desloratadine similar to that of adults receiving doses of 5 mg.
本研究旨在确定6个月及以上至2岁以下儿童使用地氯雷他定的剂量，使其单剂量目标暴露量（药时曲线下面积）与服用5mg地氯雷他定糖浆的成人相当。
在一项1期单剂量、开放标签的药代动力学研究中，58名6个月及以上至1岁以下和1岁及以上至2岁以下的儿童被随机分别给予0.625mg（1.25ml）和1.25mg（2.5ml）地氯雷他定糖浆。由于从个体受试者采集的血量有限，采用群体药代动力学方法估算地氯雷他定的药代动力学。根据筛查结果、给药后体格检查、实验室安全性检测、生命体征和不良事件评估安全性。
6个月及以上至1岁以下儿童地氯雷他定的表观清除率（CL/F）群体估算值（%变异系数）为27.8l·h⁻¹（35），1岁及以上至2岁以下儿童相应值为35.5l·h⁻¹（51），而成人为137l·h⁻¹（58）。CL/F比值（儿童与成人）表明，6个月及以上至1岁以下儿童服用1mg、1岁及以上至2岁以下儿童服用1.25mg时，全身暴露量与接受推荐剂量5mg的成人相似。地氯雷他定耐受性良好，无安全性问题。
6个月及以上至2岁以下儿童服用1.0mg和1.25mg地氯雷他定的暴露量应与接受5mg剂量的成人相似。
