Linked Life Data

9646061

Source:http://linkedlifedata.com/resource/pubmed/id/9646061

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-9-4
pubmed:abstractText
Ketoprofen is a chiral non-steroidal anti-inflammatory drug (NSAID) available as a racemic (rac) mixture of S-(+)- and R-(-)-isomers. Its inhibitory effect on prostaglandin biosynthesis resides virtually in the S-form. Interestingly, R-ketoprofen does not undergo substantial metabolic inversion in humans. Though contraindicated during the last trimester of pregnancy, NSAIDs, including ketoprofen, are used as tocolytic agents in some cases. The S/R plasma concentration ratio was reported to average 2.3 in premature neonates whose mothers were given rac-ketoprofen and to be close to 1 in the maternal plasma. Thus, we investigated the placental transfer of rac-ketoprofen in vitro using Schneider's perfused human cotyledon model. Glucosed Earle solutions with and without human serum albumin (HSA) were used. Several maternal perfusates were tested with different rac-ketoprofen concentrations together with 20 mg L-1 of antipyrine as a reference substance. Ketoprofen enantiomers were assayed by a specific HPLC method with derivatization procedure. HSA concentrations in maternal perfusate influenced the placental transfer of ketoprofen enantiomers. In the absence of HSA in the maternal perfusate, the S-(+)/R-(-) concentration ratio was close to 1 in the fetal perfusate. By contrast, this ratio averaged 1.44 after addition of HSA 10 g L-1 on the maternal side. Similar results were found for dialysis experiments using an inert Spectrapor 2 membrane suggesting that the S-(+)-free concentration is superior to the R-(-)-free concentration in the presence of HSA. Direct measurements of the free concentrations by centrifugal ultrafiltration confirmed this hypothesis. Accordingly, the data observed in vivo may result, at least in part, from the stereoselective protein binding of ketoprofen.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0767-3981
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
286-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Passage of S-(+)- and R-(-)-ketoprofen across the human isolated perfused placenta.
pubmed:affiliation
Laboratoire de Pharmacocinétique et Pharmacie Clinique, CHU Pellegrin, Bordeaux, France.
pubmed:publicationType
Journal Article, In Vitro