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

点击翻译按钮获取中文摘要

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.