Linked Life Data

2864155

Source:http://linkedlifedata.com/resource/pubmed/id/2864155

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1985-10-31
pubmed:abstractText
There is accumulating clinical evidence that 5-aminosalicylic acid (5-ASA) represents the therapeutic moiety of sulphasalazine in the treatment of inflammatory bowel disease. For more than 4 decades, the active metabolite, 5-ASA, has been administered in the form of the 'prodrug' sulphasalazine; however, in contrast to sulphasalazine, the pharmacokinetics of 5-ASA were unknown until recently. Sulphasalazine itself is poorly absorbed (3 to 12%) and its elimination half-life of about 5 to 10 hours is probably affected by the absorption process. The major part of sulphasalazine is split by bacterial azo-reduction in the colon into 5-ASA and sulphapyridine, the latter accounting for most of the adverse effects of sulphasalazine. The effective cleavage of sulphasalazine depends on an intact colon and transit time. It is markedly reduced in patients taking antibiotics and after removal of the large bowel. The formed sulphapyridine is almost completely absorbed and eliminated by hydroxylation, glucuronidation and polymorphic acetylation. Depending on the genetic phenotype, the elimination half-life and apparent oral clearance of sulphapyridine are approximately 14 hours and 40 ml/min (slow acetylators) or 6 hours and 150 ml/min (fast acetylators), respectively. Of the 5-ASA released from its 'vehicle' sulphapyridine in the colon, at least 25% is absorbed and after acetylation is subsequently excreted in the urine. At least 50% is eliminated in the faeces. Recently, 5-ASA has also been administered directly in the form of enemas, suppositories and oral slow-release preparations. While the elimination half-life of 5-ASA is short (0.5 to 1.5 h), its major acetylated metabolite (which may be active) exhibits a half-life of 5 to 10 hours. During therapy with sulphasalazine or 5-ASA, steady-state plasma concentrations of 5-ASA are relatively low (less than or equal to 2 micrograms/ml); thus its mode of action appears to be topically rather than systemically. Another approach to deliver the active 5-ASA to the gastrointestinal tract is accomplished with novel 'prodrugs' of 5-ASA, in which the carrier molecule sulphapyridine is replaced by 5-ASA itself (azodisalicylate) or other compounds.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0312-5963
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
285-302
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:2864155-Aminosalicylic Acids, pubmed-meshheading:2864155-Biological Availability, pubmed-meshheading:2864155-Chemical Phenomena, pubmed-meshheading:2864155-Chemistry, pubmed-meshheading:2864155-Colitis, pubmed-meshheading:2864155-Colon, pubmed-meshheading:2864155-Drug Interactions, pubmed-meshheading:2864155-Female, pubmed-meshheading:2864155-Half-Life, pubmed-meshheading:2864155-Humans, pubmed-meshheading:2864155-Intestinal Absorption, pubmed-meshheading:2864155-Kidney, pubmed-meshheading:2864155-Kinetics, pubmed-meshheading:2864155-Mesalamine, pubmed-meshheading:2864155-Milk, Human, pubmed-meshheading:2864155-Phenylhydrazines, pubmed-meshheading:2864155-Placenta, pubmed-meshheading:2864155-Prednisolone, pubmed-meshheading:2864155-Pregnancy, pubmed-meshheading:2864155-Rectum, pubmed-meshheading:2864155-Sulfapyridine, pubmed-meshheading:2864155-Sulfasalazine, pubmed-meshheading:2864155-Time Factors, pubmed-meshheading:2864155-Tissue Distribution
pubmed:articleTitle
Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't