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.
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