Linked Life Data

10681346

Source:http://linkedlifedata.com/resource/pubmed/id/10681346

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-4-3
pubmed:abstractText
SCH 56592 is a new broad-spectrum azole antifungal agent that is in phase 3 clinical trials for the treatment of serious systemic fungal infections. The pharmacokinetics of this drug candidate were evaluated following its intravenous (i.v.) or oral (p.o.) administration as a solution in hydroxypropyl-beta-cyclodextrin (HPbetaCD) or oral administration as a suspension in 0.4% methylcellulose (MC) in studies involving mice, rats, rabbits, dogs, and cynomolgus monkeys. SCH 56592 was orally bioavailable in all species. The oral bioavailability was higher with the HPbetaCD solution (range, 52 to approximately 100%) than from the MC suspension (range, 14 to 48%) and was higher in mice ( approximately 100% [HPbetaCD] and 47% [MC]), rats ( approximately 66% [HPbetaCD] and 48% [MC]), and dogs (72% [HPbetaCD] and 37% [MC]) than in monkeys (52% [HPbetaCD] and 14% [MC]). In rabbits, high concentrations in serum suggested good oral bioavailability with the MC suspension. The i.v. terminal-phase half-lives were 7 h in mice and rats, 15 h in dogs, and 23 h in monkeys. In rabbits, the oral half-life was 9 h. In species given increasing oral doses (mice, rats, and dogs), serum drug concentrations were dose related. Food produced a fourfold increase in serum drug concentrations in dogs. Multiple daily doses of 40 mg of SCH 56592/kg of body weight for eight consecutive days to fed dogs resulted in higher concentrations in serum, indicating accumulation upon multiple dosing, with an accumulation index of approximately 2.6. Concentrations above the MICs and minimum fungicidal concentrations for most organisms were observed at 24 h following a single oral dose in MC suspension in all five species studied (20 mg/kg for mice, rats, and rabbits and 10 mg/kg for dogs and monkeys), suggesting that once-daily administration of SCH 56592 in human subjects would be a therapeutically effective dosage regimen.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-2532389, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-3060000, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-330836, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-7712661, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-8723494, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-8843302, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-8930779, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-9021172, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-9145880, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-9210674, http://linkedlifedata.com/resource/pubmed/commentcorrection/10681346-9210684
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0066-4804
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
727-31
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Pharmacokinetics of SCH 56592, a new azole broad-spectrum antifungal agent, in mice, rats, rabbits, dogs, and cynomolgus monkeys.
pubmed:affiliation
Department of Drug Metabolism, Schering-Plough Research Institute, Kenilworth, New Jersey, USA. Amin.Nomeir@sprcorp.com
pubmed:publicationType
Journal Article, Comparative Study