Linked Life Data

710027

Source:http://linkedlifedata.com/resource/pubmed/id/710027

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1979-1-26
pubmed:abstractText
The protein binding of the new nonsteroidal anti-inflammatory agent tolmetin to human serum albumin (HSA) and to the plasma of 8 healthy subjects was studied by equilibrium dialysis at 37 degrees and pH 7.4 with 14C-tolmetin. Over the total concentration (Ct) range 3.0 to 28.7 microgram/ml (therapeutic range), the fraction of tolmetin unbound to 4% HSA was largely invariant at 0.3%. At 100 microgram/ml the unbound fraction rose to 0.8 and at 434 microgram/ml to 3.6%. Within the therapeutic concentration range, tolmetin binding to 0.4% HSA was reduced in accordance with the law of mass action and at Ct = 26.2 microgram/ml, 10.5% was free. Analysis of the 0.4% HSA data showed tolmetin had 3 classes of binding sites (n1 = 1, K1 = 8.3 X 10(5) M-1; n2 = 4, K2 = 2.4 X 10(4) M-1; n3 = 44, K1 = 7.9 X 10(1) M-1). By studying the binding to 0.4% HSA at 23 degrees, it was established that the free energy change in binding for the first two classes of sites was entirely entropic in nature. Albumin accounted for almost all the binding of tolmetin in human plasma. The effect of other drugs, the tolmetin metabolite McN 2987 (5-p-carboxybenzoyl-1-methylpyrrole-2-acetic acid), tryptophan, and oleic acid on tolmetin binding to 4% HSA was studied using ultrafiltration and 14C-tolmetin. Aspirin and salicyclic acid decreased tolmetin binding and a combination of aspirin and salicyclic acid exerted a synergistic displacing effect. Indomethacin and ibuprofen had no effect while phenylhbutazone and acetaminophen increased tolmetin binding slightly. Tolmetin binding was decreased slightly by McN 2987 and tryptophan and markedly increased by oleic acid. McN 2987 was not bound as extensively as tolmetin. Binding of 14C-tolmetin to the plasma of 4 arthritic patients was studied by ultrafiltration and found to be less than to normal plasma and 4% HSA. Distribution of tolmetin in the whole blood of 8 healthy subjects using a centrifugation technique showed that the drug was not taken up by red blood cells at therapeutic concentrations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0009-9236
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
694-705
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1978
pubmed:articleTitle
Protein binding of tolmetin.
pubmed:publicationType
Journal Article, In Vitro