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标题：Comparative Absorption of 5-Aminosalicylic Acid (5-ASA) after Administration of a 5-ASA Enema and Salazosulfapyridine (SASP) after an SASP Suppository in Japanese Volunteers
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作者：Kenji Tokui ; Yoshitaka Asai ; Toshiharu Arakawa 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2002
卷号：25
期号：2
页码：264-267
DOI：10.1248/bpb.25.264
出版社：The Pharmaceutical Society of Japan
摘要：Salazosulfapyridine (SASP) is widely used orally and rectally in the treatment of ulcerative colitis. SASP is mainly metabolized by hydrolysis and the main active metabolite, 5-aminosalicylic acid (5-ASA), has an antiinflammatory effect. In the present study, we prepared suppositories containing 6.5 mmol of SASP and an enema containing 6.5 mmol of 5-ASA. We measured the concentrations of SASP and its various metabolites, 5-ASA, sulfapyridine (SP), acetylated metabolite of SP (Ac-SP), and N -acetyl-5-ASA (Ac-5-ASA), in the serum and urine after a single administration of each preparation to healthy male volunteers. When the SASP suppository was administered, the maximum concentration ( C _max) of SASP and Ac-5-ASA was 2.5±0.4 and 0.5±0.2 µM and the time to C _max ( T _max) was 5 and 12 h, respectively. The C _max value of SP, which causes side effects, was one-half of that of the parent compound. No 5-ASA in the serum was observed. When the 5-ASA enema was administered, C _max and T _max values of 5-ASA and Ac-5-ASA were 5.8±2.0 and 13.3±3.6 µM and 1 and 7 h, respectively. The area under the serum concentration–time curve ( AUC ) of SASP was 27.4±4.8 µM·h, a finding similar to that of 5-ASA after the administration of the 5-ASA enema (29.4±11.1 µM·h). The percentage of urinary recovery of SASP 24 h after administration of the SASP suppository was approximately 0.2%. These results indicate that SASP administered rectally is almost completely hydrolyzed in the colon and that 5-ASA is partially absorbed from the small intestine in unchanged form. On the other hand, approximately 0.3% of 5-ASA was recovered in the urine in unchanged form after the administration of the 5-ASA enema, whereas the urinary recovery of Ac-5-ASA was more than 10%. The present findings suggest that 5-ASA has favorable absorptive properties and can be expected to have systemic action after rectal administration of a 5-ASA enema.
关键词：5-aminosalicylic acid;salazosulfapyridine;enema;suppository;pharmacokinetic