Linked Life Data

3874742

Source:http://linkedlifedata.com/resource/pubmed/id/3874742

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1985-9-11
pubmed:abstractText
When 100 mg oral zomepirac was taken with 500 mg b.i.d. oral probenecid by six healthy subjects, the disposition of zomepirac was markedly altered. Probenecid decreased total plasma clearance of zomepirac by 64%, which resulted in an increase in bioavailability from 0.55 without probenecid to 0.84 when given concurrently. The apparent metabolic clearance of zomepirac to form zomepirac acyl glucuronide was reduced 71% and zomepirac renal clearance, a minor elimination route, was reduced by 79%. When assayed by a method that prevents degradation of the labile acyl glucuronide, zomepirac glucuronide concentrations in plasma were comparable to those of zomepirac. Probenecid decreased the renal clearance of zomepirac glucuronide by 72%, which, together with the increased zomepirac levels, resulted in a 2.8-fold increase in the AUC of the conjugate. Urinary excretion of zomepirac glucuronide was reduced from 72% to 58% of the dose, but the excretion of free zomepirac was unchanged at 5% of the dose. The ratio of the total clearance/bioavailability of zomepirac in control subjects was 682 +/- 246 ml/min, which is double the value reported in previous studies of zomepirac disposition. We believe that this difference is due to degradation of the unstable zomepirac acyl glucuronide in the previous analytic methodologies used. Qualitatively, the effects of probenecid on zomepirac disposition are similar to those previously reported for other drugs of this class that are metabolized to acyl glucuronides. However, zomepirac appears unusual in that significant levels of its acyl glucuronide metabolite are found in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0009-9236
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
121-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1985
pubmed:articleTitle
Effect of probenecid on the formation and elimination of acyl glucuronides: studies with zomepirac.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't