Abstract
A series of experiments has been performed in healthy male volunteers to investigate the disposition of orally administered disodium azodisalicylate, a potentially useful drug for the treatment of ulcerative colitis. The drug was given by mouth in doses of up to 2 g a day for six weeks and there were no adverse effects. Serum concentrations of the intact compound were low and the serum half-time was 4-12.8 days, probably because of a combination of a low clearance rate and a high apparent volume of distribution. Less than 5% of the ingested dose was excreted unchanged in the urine. Circulating concentrations of 5-ASA and N-acetyl-5-ASA were low and 30% of the equivalent daily dose was excreted in the urine, predominantly as N-acetyl-5-ASA. In most subjects more than 30% of the equivalent daily dose of 5-ASA was recovered from the faeces, either as 5-ASA itself or as the acetylated derivative. As 5-ASA has been shown to be the active therapeutic moiety of sulphasalazine, disodium azodisalicylate appears to be suitable for therapeutic trial in ulcerative colitis.
MeSH Terms
Adult
Aged
Aminosalicylic Acids/administration & dosage,adverse effects,metabolism
Colitis, Ulcerative/drug therapy
Drug Administration Schedule
Feces/analysis
Half-Life
Humans
Kidney/metabolism
Kinetics
Male
Middle Aged
Chemicals
Aminosalicylic Acids
olsalazine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Willoughby C P
Aronson J K
Agback H
Bodin N O
Truelove S C
References (11)
11 references, click to expand
-
Absorption, metabolism, and excretion of salicylazosulfapyridine in man.
Clin Pharmacol Ther. 1972 Jul-Aug;13(4):539-51
PMID: 4402886
-
Distribution studies of salicylazosulfapyridine and its metabolites.
Gastroenterology. 1973 Feb;64(2):240-5
PMID: 4405598
-
Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype.
N Engl J Med. 1973 Sep 6;289(10):491-5
PMID: 4146729
-
A controlled therapeutic trial of long-term maintenance treatment of ulcerative colitis with sulphazalazine (Salazopyrin).
Gut. 1973 Dec;14(12):923-6
PMID: 4150435
-
An experiment to determine the active therapeutic moiety of sulphasalazine.
Lancet. 1977 Oct 29;2(8044):892-5
PMID: 72239
-
Active therapeutic moiety of sulphasalazine.
Lancet. 1978 Feb 4;1(8058):277
PMID: 74700
-
Optimum dose of sulphasalazine for maintenance treatment in ulcerative colitis.
Gut. 1980 Mar;21(3):232-40
PMID: 6105118
-
The effect of topical N-acetyl-5-aminosalicylic acid in ulcerative colitis.
Scand J Gastroenterol. 1980;15(6):715-9
PMID: 7010522
-
The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man.
Br J Clin Pharmacol. 1982 Apr;13(4):523-8
PMID: 6121576
-
Sulphasalazine and salicylazosulphadimidine in ulcerative colitis.
Lancet. 1962 May 26;1(7239):1094-6
PMID: 13865153
-
CONTROLLED TRIAL OF SULPHASALAZINE IN THE TREATMENT OF ULCERATIVE COLITIS.
Gut. 1964 Oct;5:437-42
PMID: 14218553