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Colonic Azodisalicylate Metabolism Determined by In Vivo Dialysis in Healthy Volunteers and Patients With Ulcerative Colitis
- Source :
- Gastroenterology. 86:1496-1500
- Publication Year :
- 1984
- Publisher :
- Elsevier BV, 1984.
-
Abstract
- Azodisalicylate, a second generation drug of sulfasalazine, delivers twice the amount of 5-aminosalicylic acid to the colonic lumen on a molar basis when split by bacterial azoreductases. In 6 patients with inactive ulcerative colitis, the colonic metabolism of sulfasalazine and azodisalicylate was studied by equilibrium in vivo dialysis of feces to measure the therapeutically relevant concentrations of their metabolites (5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid) in free fecal water. After oral intake of sulfasalazine (2 g/day) the total luminal concentrations of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid determined by high-performance liquid chromatography were higher (median 14 mmol/L) than previously reported and almost doubled (median 25 mmol/L, p less than 0.05) when sulfasalazine was replaced by the same dose of azodisalicylate. In contrast, the corresponding serum concentrations were negligible. After administration of azodisalicylate to 12 healthy volunteers, a similar distribution of the metabolites was found. In nearly all cases, the concentrations of azodisalicylate in fecal dialysates were below the detection limit (6 mumol/L). We conclude, therefore, that oral azodisalicylate is a highly effective means of delivery of 5-aminosalicylic acid to the colonic mucosa. In addition, determination of the active metabolites in free fecal water seems important for the interpretation of results obtained in vitro concerning the mode of drug action.
- Subjects :
- Adult
Male
medicine.medical_specialty
Aminosalicylic acid
Colon
medicine.medical_treatment
Gastroenterology
Feces
chemistry.chemical_compound
In vivo
Sulfasalazine
Internal medicine
medicine
Humans
Chromatography, High Pressure Liquid
Dialysis
Olsalazine
Hepatology
business.industry
Metabolism
Middle Aged
medicine.disease
Ulcerative colitis
Aminosalicylic Acids
Biochemistry
chemistry
Colitis, Ulcerative
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 00165085
- Volume :
- 86
- Database :
- OpenAIRE
- Journal :
- Gastroenterology
- Accession number :
- edsair.doi.dedup.....edd60335dfe0456eefeff3fba8951610