RIDOGREL IN CLINICALLY STABLE, NON ACTIVE ULCERATIVE COLITIS PEDS PAT

炎症性肠病(IBD)表现为一组影响小肠(克罗恩病)或结肠(溃疡性结肠炎或UC)粘膜的炎症性疾病。这两种疾病都影响儿科人群；然而，回顾儿科发表的关于IBD的信息，该领域的意见领袖对于克罗恩病和UC在儿童中的平均发病年龄、发病率和患病率显然缺乏共识。也有人建议，由于医生可能不愿意让儿童接受放射、内窥镜和活组织检查，除非他们是急性疾病，否则15岁以下人群的真实发病率可能被严重低估。由于儿童和成人患者的IBD表现和发病机制相似，而儿童缺乏临床研究，因此对儿童人群中可用治疗加州大学伯克利分校和克罗恩病的指南是从成人患者的研究中推断出来的。认为在IBD中起作用的主要因素是感染性因素和宿主易感性改变(即细胞介导的免疫或T细胞抑制活性和单核巨噬细胞功能障碍)。前列腺素(PG)和白三烯(LTS)与包括IBD在内的许多炎症状态有关。IBD患者的直肠黏膜产生异常高水平的血栓素A2(TXA2)，而前列腺素I2(PGI2)水平不受影响或升高。血栓素可能在IBD中起主要致病作用。在低剂量时，雷公藤能特异性地抑制血栓素合成酶。在人体内，利格雷在口服后被完全吸收，首过代谢可以忽略不计。利多格雷似乎不是通过细胞色素P450酶代谢的。初步数据显示，可能与过氧化物体途径有关。到目前为止，还没有关于成人和儿童在过氧化体代谢方面的潜在差异的信息。这项试验的主要目的是描述单剂量口服2.5或5.0 mg雷格雷在8岁至18岁的UC儿童患者中的药代动力学。第二个目标是评估口服利格雷2.5 mg或5.0 mg治疗儿童溃疡性结肠炎的安全性和耐受性(不良反应)。这是一项平行分组设计的多中心、单盲、随机、药代动力学试验。有资格进入研究并接受随机试验药物的患者将按年龄分为两组：8岁至13岁和13岁至18岁。两组患者都将接受监测，并在服药后24小时内接受实验室评估。药代动力学(PK)评估被安排在研究给药之前和之后的24小时内。尿PK参数将在同一时期进行评估。在这个中心，我们总共招募了五(5)名患者。在这些人中，三(3)人已经完成了研究。两(2)名患者筛查失败，因此他们没有服药。不良事件包括：头痛(1)[被确定与研究药物有关]，以及静脉插管部位疼痛(1)，与药物无关。目前，这项研究仍在进行中，我们计划在来年再招募10名患者。GCRC将用于PK抽样和监测食物消费。

Inflammatory Bowel Disease (IBD) is represented by a group of inflammatory conditions affecting the mucosa of the small intestine (Crohn's Disease) or colon (Ulcerative Colitis or UC). Both diseases affect the pediatric population; however, review of the published information on IBD in pediatrics reveals a definite lack of consensus amongst the opinion leaders in this field regarding the mean age of onset, incidence, and prevalence rates of Crohn's and U.C. in children. It is also suggested that since physicians may be reluctant to submit children to radiological, endoscopic, and biopsy procedures unless they are acutely ill, the true incidence may be significantly underestimated for the population under the age of 15. Because the IBD presentation and pathogenesis is similar in both pediatric and adult patients, and clinical studies in children are lacking, the guidelines for use of the available therapies for both U.C. and Crohn's disease in the pediatric population have been extrapolated from studies in adult patients. The major factors thought to play a rold in IBD are infectious agents and altered host susceptibility (i.e., impaired cell mediated immunity or T-cell suppressor activity and monocyte-macrophage dysfunction). Prostaglandins (PGs) and leukotrienes (LTs) have been implicated in many inflammatory conditions, including IBD. The rectal mucosa of patients with IBD produce abnormally high levels of thromboxane A2 (TXA2), while prostaglandin I2 (PGI2) levels are unaffected or increased. Thromboxanes may play a major pathogenic role in IBD. At low doses, ridogrel specifically inhibits the enzyme thromboxane synthetase. In man, ridogrel is completely absorbed after oral administration with negligible first-pass metabolism. Ridogrel does not appear to be metabolized through cytochrome P450 enzymes. Preliminary data suggest that peroxisomal pathways may be involved. To date, no information is available on potential differences in peroxisomal metabolism comparing adults and children. The primary objective of this trial is to characterize the pharmacokinetics of a single oral dose of 2.5 or 5.0 mg ridogrel in pediatric patients age 8 to <18 with UC. The secondary objective is to evaluate the safety and tolerability (adverse experiences) of oral ridogrel 2.5 mg or 5.0 mg given to pediatric patients with ulcerative colitis. This is a multicenter, single-blind, randomized, pharmacokinetic trial with a parallel group design. Patients who qualify to enter the study and receive randomized test drug will be stratified into two groups by age: >8 to <13 and >13 to <18. Both groups will be monitored and undergo laboratory evaluations for the subsequent 24 hours after dosing. Pharmacokinetic (PK) evaluations are scheduled just prior to study drug administration and for 24 hours afterward. Urinary PK parameters will be evaluated over the same period. At this center, we have enrolled a total of five (5) patients. Of these, three (3) have completed the study. Two (2) patients were screen failures, thus they were not dosed. Adverse events included: headache (1) [which was determined to be related to study drug], and pain at the IV insertion site (1) that was not related to drug. At this time, the study remains open and we plan to enroll an additional 10 patients in the coming year. The GCRC will be used for the PK sampling and to monitor food consumption.