Gastroenterology Department, NorthShore University HealthSystem, Highland Park, Illinois, USA.
Inflamm Bowel Dis. 2013 Feb;19(2):301-8. doi: 10.1002/ibd.23003.
5-Aminosalicylate (5-ASA) formulations are approved for the treatment of ulcerative colitis (UC). Determination of the colonic pharmacokinetics of 5-ASA is challenging. A dynamic model of 5-ASA colonic amounts after oral delayed-release 5-ASA (Asacol), oral extended delayed-release 5-ASA (Lialda), 5-ASA enema (Rowasa), foam and suppositories (Canasa) was developed to determine the colonic kinetics of these agents.
We created a model with Stella software. Colonic 5-ASA in the right, transverse, descending, sigmoid colon, and rectum were estimated for adults after recommended doses of the above formulations. Simulations of active mild/moderate UC and in remission were performed and compared using Student's t-test for differences in means.
For UC in remission, the highest amounts of 5-ASA were from Asacol in the right and transverse colon (P < 0.01), Lialda in the descending and sigmoid colon (P < 0.01), and Rowasa in the rectum (P < 0.01). For active UC, sigmoid amounts were highest with foam (P < 0.01), and rectal amounts highest with Rowasa (P < 0.01). Differences in rectosigmoid amounts of 5-ASA from enemas and suppositories for UC in remission occurred based on the relationship between the timing of administration relative to the daily bowel movement (P < 0.01).
Compared to Asacol, Lialda results in higher 5-ASA amounts in the left colon. Asacol with Rowasa provides highest 5-ASA amounts across the entire colon. Higher 5-ASA amounts from topical formulations occur when the insertion occurs soon after the daily bowel movement. This model provides a rationale for further investigation.
5-氨基水杨酸（5-ASA）制剂被批准用于治疗溃疡性结肠炎（UC）。5-ASA 的结肠药代动力学的测定具有挑战性。建立了一个口服迟释 5-ASA（Asacol）、口服延长迟释 5-ASA（Lialda）、5-ASA 灌肠剂（Rowasa）、泡沫剂和栓剂（Canasa）后 5-ASA 结肠量的动态模型，以确定这些药物的结肠动力学。
我们使用 Stella 软件创建了一个模型。对于成人，在上述制剂推荐剂量后，估计右、横、降、乙状结肠和直肠的结肠 5-ASA。对缓解期和活动期轻度/中度 UC 进行了模拟，并使用学生 t 检验比较了差异。
对于缓解期 UC，右、横结肠中 5-ASA 含量最高的是 Asacol（P < 0.01），降、乙状结肠中含量最高的是 Lialda（P < 0.01），直肠中含量最高的是 Rowasa（P < 0.01）。对于活动期 UC，泡沫剂的乙状结肠含量最高（P < 0.01），Rowasa 的直肠含量最高（P < 0.01）。缓解期 UC 灌肠剂和栓剂的直肠乙状结肠 5-ASA 量的差异与给药时间与每日排便时间的关系有关（P < 0.01）。
与 Asacol 相比，Lialda 使左结肠中的 5-ASA 含量更高。Asacol 联合 Rowasa 可使整个结肠获得最高的 5-ASA 含量。在每日排便后不久进行插入时，局部制剂的 5-ASA 含量更高。该模型为进一步研究提供了依据。
