Linked Life Data

9435165

Source:http://linkedlifedata.com/resource/pubmed/id/9435165

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-2-11
pubmed:abstractText
Topotecan is primarily eliminated by the kidneys, with 60 to 70% of the dose recovered as topotecan total in the urine. To elucidate the mechanisms of topotecan renal clearance, we evaluated the effect of probenecid on topotecan renal and systemic disposition in mice. Topotecan lactone or hydroxy acid (1.25 mg/kg i.v.) was administered alone or in combination with probenecid (600 or 1,200 mg/kg) given by oral gavage 30 min before and 3 hr after topotecan. Serial blood samples (three mice per time point) and urine samples (five mice per treatment arm) were collected during a 6-hr period. Compared with topotecan alone, coadministration of topotecan lactone or hydroxy acid with probenecid (600 mg/kg) decreased topotecan lactone, total, and hydroxy acid systemic clearance, and total renal clearance. The predominant effect of probenecid was to increase hydroxy acid area under the plasma concentration time curve after administration of topotecan lactone (238.8 vs. 109.9 ng.hr/ml alone, P < .05), or hydroxy acid (1297.2 vs. 355.0 ng.hr/ml alone, P < .05). By inhibiting renal tubular secretion, probenecid decreased renal and systemic clearance which led to an increase in topotecan systemic exposure. These data suggest that probenecid primarily inhibited secretion of the anionic hydroxy acid form, and by direct or indirect mechanisms increased topotecan lactone systemic exposure. Topotecan elimination through renal tubular secretion may have clinical relevance for the use of topotecan in patients with altered renal function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
89-94
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Probenecid alters topotecan systemic and renal disposition by inhibiting renal tubular secretion.
pubmed:affiliation
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't