Linked Life Data

11891672

Source:http://linkedlifedata.com/resource/pubmed/id/11891672

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-3-13
pubmed:abstractText
BMS-204352, a maxi-K channel opener, is currently under development for the treatment of stroke. The objective of this study was to determine the pharmacokinetics, mass balance and absolute oral bioavailability of [(14)C]-BMS-204352 in rats and dogs. [(14)C]-BMS-204352 was administered, to rats (n=10/group; parallel design, 6 mg/kg) and dogs (n=4/group; crossover design, 2 mg/kg), as an oral (PO) or as a 3-min intraarterial (IA) infusion in rats and a 6-min intravenous (i.v.) infusion in dogs. Blood, urine, and feces samples were collected and analyzed for unchanged BMS-204352 (plasma) using a validated LC/MS assay and for total radioactivity (plasma, urine, feces) using liquid scintillation counting. The mean total body clearance (CLT) and steady-state volume of distribution (VSS) values for the unchanged BMS-204352 were 2.58 +/- 0.48 l/h/kg and 6.3 +/- 1.14 l/kg, respectively, in rats and 0.21 +/- 0.02 l/h/kg and 4.06 +/- 0.47 l/kg, respectively, in dogs. In both species, the elimination half-life of total radioactivity was significantly longer as compared to the unchanged drug. After IA administration of radiolabeled BMS-204352 to rats, ca. 5.9 and 85% of radioactivity was recovered within 7 days in urine and feces, respectively; corresponding recoveries after PO dosing were 4.5 and 99.5%, respectively. The recoveries were similar in dogs, i.e., ca. 5.2 and 83% of administered radioactivity recovered in urine and feces, respectively, for IV dose and ca. 4 and 86%, respectively, for PO dose. These data indicate that nonrenal (biliary) elimination in both species was predominant. Based on comparable urinary recovery of radioactivity and plasma AUCs of radioactivity, the extent of oral absorption of BMS-204352 appeared to be complete in both species. The absolute oral bioavailability was 55% in rats and 79% in dogs. Bioavailability and extent of absorption data suggest evidence of first pass metabolism of BMS-204352 in the rat and dog.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0142-2782
pubmed:author
pubmed:copyrightInfo
Copyright 2002 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-6
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Disposition of radiolabeled BMS-204352 in rats and dogs.
pubmed:affiliation
Clinical Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08540, USA. rajesh.krishna@bms.com
pubmed:publicationType
Journal Article