A RANDOMIZED, OPEN-LABEL, PARALLEL-GROUP STUDY TO DETERMINE THE PHARMACOKINET

确定 PHARMACOKINET 的随机、开放标签、平行组研究

• 批准号: 7950625
• 负责人: GEORGE D FERRY
• 金额: $ 0.03万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950625
• 关键词: 17 year old; 9 year old; Abdominal Pain; Adolescent; Adult; Age; Body Weight decreased; Characteristics; Child; Childhood; Clinical; Clinical Research; Colon; Computer Retrieval of Information on Scientific Projects Database; Data; Diagnosis; Diarrhea; Diffuse; Disease; Distal part of ileum; Dose; Drug Kinetics; Excretory function; Fever; Funding; Grant; Hemorrhage; Hour; Inflammation; Inflammatory Bowel Diseases; Institution; Intestines; Lead; Literature; Measures; Medical; Mesalamine; Metabolism; Oral Administration; Patients; Performance; Pharmaceutical Preparations; Physiological; Population; Property; Randomized; Relative (related person); Research; Research Personnel; Resources; Safety; Source; Symptoms; Tablets; Time; Ulcerative Colitis; United States National Institutes of Health; absorption; design; gastrointestinal; interest; open label; rectal; tablet formulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HYPOTHESIS This study will provide information about the pharmacokinetics of mesalamine and its major metabolite in children being treated with Asacol for mildly to moderately active ulcerative colitis. We hypothesize that more in depth pharmacokinetic analysis of mesalamine in children and adolescents receiving this drug will lead to better understanding of adequate and safe dosing in this population. SPECIFIC AIMS The primary objective of this study is to characterize mesalamine pharmacokinetics following 28 days of oral administration of 30 mg/kg, 60 mg/kg, or 90 mg/kg of mesalamine, given in divided doses every 12 hours as Asacol 400 mg tablets, to patients with ulcerative colitis who are 5 to 17 years of age. Secondary objectives are to obtain safety and tolerability data concerning the use of mesalamine in patients with ulcerative colitis who are 5 to 17 years of age. BACKGROUND AND SIGNIFICANCE Ulcerative colitis is a type of inflammatory bowel disease characterized by diffuse, continuous inflammation of the colon. Recent estimates suggest that approximately 17,000 children between 5 and 17 years of age in the U.S. are diagnosed with ulcerative colitis.1 2 3 Estimates of average age at onset in children vary, although 80-90% of patients are 9 years of age or older when symptoms develop. Evidence from the medical literature suggests that the clinical course and manifestations of ulcerative colitis are similar in children and adults.6 7 8 The most consistent symptoms of ulcerative colitis (diarrhea, abdominal pain, rectal bleeding, fever, and weight loss) are found in comparable proportions in both children and adults with the disease, and are more dependent on the disease activity than age. Asacol¿ is a delayed-release tablet formulation designed to deliver mesalamine (also known as mesalazine) at a pH = 7.0. This property results in release of the drug in the terminal ileum and beyond. Physiologic factors such as the pH of the surrounding medium, transit times in the intestinal regions of interest, and the rate and extent of absorption and metabolism govern Asacol drug release and delivery, which in turn influence the pharmacokinetic profile of the delivered drug. These physiologic factors and their effect on Asacol pharmacokinetics have been studied in adults, but corresponding studies in children have not been performed. However, relevant studies describing the gastrointestinal pH; transit times; and pharmacokinetic aspects of drug absorption, metabolism, and excretion in pediatric patients (relative to adults) provide reasons to expect that the performance characteristics of Asacol in the pediatric population will be similar to those measured in adults.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 假设 本研究将提供关于美沙拉嗪及其主要代谢产物在接受Asacol治疗的轻度至中度活动性溃疡性结肠炎儿童中的药代动力学信息。我们假设，对接受美沙拉嗪的儿童和青少年进行更深入的药代动力学分析，将有助于更好地了解该人群的适当和安全剂量。 具体目标 本研究的主要目的是描述5 - 17岁溃疡性结肠炎患者口服30 mg/kg、60 mg/kg或90 mg/kg美沙拉嗪（Asacol 400 mg片剂，每12小时分次给药）28天后的药代动力学特征。 次要目的是获得5 - 17岁溃疡性结肠炎患者使用美沙拉嗪的安全性和耐受性数据。 背景和意义 溃疡性结肠炎是一种炎症性肠病，其特征在于结肠的弥漫性、持续性炎症。 最近的估计表明，美国约有17，000名5至17岁的儿童被诊断患有溃疡性结肠炎。1 2 3儿童平均发病年龄的估计值各不相同，尽管80-90%的患者在出现症状时为9岁或以上。 来自医学文献的证据表明，溃疡性结肠炎的临床病程和表现在儿童和成人中相似。6 7 8溃疡性结肠炎最一致的症状（腹泻、腹痛、直肠出血、发热和体重减轻）在儿童和成人中的比例相当，并且更依赖于疾病活动而不是年龄。 Asacol是一种延迟释放片剂，旨在在pH = 7.0时提供美沙拉嗪（也称为美沙拉嗪）。 该性质导致药物在回肠末端及更远处释放。 生理因素，如周围介质的pH值，在感兴趣的肠道区域的通过时间，以及吸收和代谢的速率和程度，控制Asacol药物释放和递送，这反过来又影响递送药物的药代动力学特征。 已在成人中研究了这些生理因素及其对Asacol药代动力学的影响，但尚未在儿童中进行相应的研究。 然而，描述儿科患者（相对于成人）的胃肠道pH值、通过时间和药物吸收、代谢和排泄的药代动力学方面的相关研究提供了预期Asacol在儿科人群中的性能特征与在成人中测量的性能特征相似的理由。