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

Kenji Tokui, Yoshitaka Asai, Toshiharu Arakawa, Takatoshi Matsumoto, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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Abstract

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 m mol 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 (Cmaz) of SASP and Ac-5-ASA was 2.5±0.4 and 0.5±0.2 μM and the time to Cmax (Tmax) was 5 and 12 h, respectively. The Cmax 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 Tmax values of 5-ASA and Ac-5-ASA were 5.8±2.0 and 13.3±3.6 μM and 1 and 7h, 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.

Original languageEnglish
Pages (from-to)264-267
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Volume25
Issue number2
DOIs
Publication statusPublished - 01-02-2002
Externally publishedYes

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Mesalamine
Sulfasalazine
Suppositories
Enema
Volunteers
Sulfapyridine
Serum
Urine
Rectal Administration
Ulcerative Colitis
Small Intestine
Area Under Curve

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

@article{468d739e9f2e47bab793cac15f39fd6b,
title = "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",
abstract = "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 m mol 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 (Cmaz) of SASP and Ac-5-ASA was 2.5±0.4 and 0.5±0.2 μM and the time to Cmax (Tmax) was 5 and 12 h, respectively. The Cmax 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 Tmax values of 5-ASA and Ac-5-ASA were 5.8±2.0 and 13.3±3.6 μM and 1 and 7h, 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.",
author = "Kenji Tokui and Yoshitaka Asai and Toshiharu Arakawa and Takatoshi Matsumoto and Toshitaka Nabeshima",
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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. / Tokui, Kenji; Asai, Yoshitaka; Arakawa, Toshiharu; Matsumoto, Takatoshi; Nabeshima, Toshitaka.

In: Biological and Pharmaceutical Bulletin, Vol. 25, No. 2, 01.02.2002, p. 264-267.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Tokui, Kenji

AU - Asai, Yoshitaka

AU - Arakawa, Toshiharu

AU - Matsumoto, Takatoshi

AU - Nabeshima, Toshitaka

PY - 2002/2/1

Y1 - 2002/2/1

N2 - 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 m mol 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 (Cmaz) of SASP and Ac-5-ASA was 2.5±0.4 and 0.5±0.2 μM and the time to Cmax (Tmax) was 5 and 12 h, respectively. The Cmax 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 Tmax values of 5-ASA and Ac-5-ASA were 5.8±2.0 and 13.3±3.6 μM and 1 and 7h, 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.

AB - 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 m mol 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 (Cmaz) of SASP and Ac-5-ASA was 2.5±0.4 and 0.5±0.2 μM and the time to Cmax (Tmax) was 5 and 12 h, respectively. The Cmax 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 Tmax values of 5-ASA and Ac-5-ASA were 5.8±2.0 and 13.3±3.6 μM and 1 and 7h, 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.

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DO - 10.1248/bpb.25.264

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