{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670319720951168.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1046/j.1365-2125.1999.00046.x"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2125.1999.00046.x"}},{"identifier":{"@type":"URI","@value":"https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2125.1999.00046.x"}}],"dc:title":[{"@value":"Stereoselective pharmacokinetics of ketoprofen and ketoprofen glucuronide in end‐stage renal disease: evidence for a ‘futile cycle’ of elimination"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p> <jats:italic>\n            \n\t\t\t\t\t\tAims</jats:italic> To assess if futile cycling of ketoprofen occurs in patients with decreased renal function.</jats:p><jats:p> <jats:italic>\n            \n\t\t\t\t\t\tMethods</jats:italic> Ketoprofen was administered to six haemodialysis‐dependent patients with end‐stage renal disease as single (50 mg) or multiple doses (50 mg three times daily, for 7 days). Plasma and dialysate concentrations of the unconjugated and glucuronidated R‐ and S‐enantiomers of ketoprofen were determined using h.p.l.c. following the single and multiple dosing.</jats:p><jats:p> <jats:italic>\n            \n\t\t\t\t\t\tResults The oral clearance was decreased and terminal elimination half‐lives of R‐ and S‐ketoprofen and the corresponding acyl glucuronides were increased in functionally anephric patients compared with healthy subjects. In contrast with the R‐isomers, S‐ketoprofen and S‐ketoprofen glucuronide exhibited an unexpected accumulation (2.7–3.8 fold) after repeated dosing achieving S:R ratios of 3.3±1.7 and 11.2±5.3, respectively. The plasma dialysis clearances for R‐ and S‐ketoprofen glucuronides were 49.4±19.8 and 39.0±15.9 ml min<jats:sup>−1</jats:sup>, respectively, and 10.8±17.6 and 13.3±23.5 ml min<jats:sup>−1</jats:sup></jats:italic> for unconjugated R‐ and S‐ketoprofen.</jats:p><jats:p> <jats:italic>\n            \n\t\t\t\t\t\tConclusions</jats:italic> The selective accumulation of S‐ketoprofen and its acyl glucuronide are consistent with amplification of chiral inversion subsequent to futile cycling between R‐ketoprofen and R‐ketoprofen glucuronide. Severe renal insufficiency, and possibly more modest decrements, results in a disproportionate increase in systemic exposure to the S‐enantiomer which inhibits both pathologic and homeostatic prostaglandin synthesis.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380851344607091971","@type":"Researcher","foaf:name":[{"@value":"Grubb"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319720951169","@type":"Researcher","foaf:name":[{"@value":"Rudy"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319720951170","@type":"Researcher","foaf:name":[{"@value":"Brater"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319720951171","@type":"Researcher","foaf:name":[{"@value":"Hall"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"03065251"},{"@type":"EISSN","@value":"13652125"}],"prism:publicationName":[{"@value":"British Journal of Clinical Pharmacology"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"1999-10","prism:volume":"48","prism:number":"4","prism:startingPage":"494","prism:endingPage":"500"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2125.1999.00046.x"},{"@id":"https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2125.1999.00046.x"}],"createdAt":"2003-03-11","modifiedAt":"2023-10-28","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1390282680156014720","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Separation and Determination of Diastereomeric Flurbiprofen Acyl Glucuronides in Human Urine by LC/ESI-MS with a Simple Column-Switching Technique"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1046/j.1365-2125.1999.00046.x"},{"@type":"CROSSREF","@value":"10.2133/dmpk.17.142_references_DOI_Ce7AcFLRnaU4Q1F4DD8ktcJL4dQ"}]}