Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.
Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.
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DOI：
10.2147/dddt.s95316
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Martin P
中科院分区：
文献类型：
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作者：
Cuffari C;Pierce D;Korczowski B;Fyderek K;Van Heusen H;Hossack S;Wan H;Edwards AY;Martin P
关于美沙拉嗪（5-氨基水杨酸; 5-阿萨）用于儿童溃疡性结肠炎（UC）的数据有限。评价UC儿童和青少年每日一次口服美沙拉嗪多基质后5-阿萨及其代谢产物乙酰基-5-阿萨（Ac-5-阿萨）的药代动力学和安全性特征。UC受试者（5-17岁; 18-82 kg，按体重分层）接受多基质美沙拉嗪30、60或100 mg/kg/天，每日一次（至4，800 mg/天），持续7天。在第5天和第6天给药前采集血样。在第7天和第8天，采集血液和尿液样本并评价安全性。5-阿萨和Ac-5-阿萨血浆和尿液浓度通过非房室方法进行分析，并用于开发群体药代动力学模型。52例受试者（21例[30 mg/kg]; 22例[60 mg/kg]; 9例[100 mg/kg]）接受随机化。第7天，30和60 mg/kg/天队列中5-阿萨和Ac-5-阿萨的全身暴露量呈剂量比例性增加。对于30、60和100 mg/kg/天剂量，5-阿萨吸收的平均百分比分别为29.4%、27.0%和22.1%。5-阿萨和Ac-5-阿萨的模拟稳态暴露量和变异性（变异系数分别约为50%和40%-45%）与之前在成人中观察到的剂量相似。10例受试者报告了治疗后出现的不良事件。不同剂量和年龄组之间的事件相似，未发现新的安全性信号。接受美沙拉嗪多基质治疗的UC儿童和青少年显示5-阿萨和Ac-5-阿萨的药代动力学特征与历史成人数据相似。在所有剂量和年龄组中，美沙拉嗪多基质耐受性良好。ClinicalTrials.gov标识符：NCT 01130844。
Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. Participants (5–17 years of age; 18–82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844.