Matches in SemOpenAlex for { <https://semopenalex.org/work/W2339548077> ?p ?o ?g. }
Showing items 1 to 86 of
86
with 100 items per page.
- W2339548077 endingPage "471" @default.
- W2339548077 startingPage "471" @default.
- W2339548077 abstract "2044 CDDO (2-cyano,3,12-dioxoolean-1,9 (11)-dien-28-oic acid; NSC-711193) is a synthetic oleanane triterpenoid that has been shown to have potent differentiating, anti-proliferative, and anti-inflammatory activities both in vitro and in vivo. In preparation for clinical trials, the pharmacokinetics and toxicity of CDDO were investigated in groups of male Fischer rats (4 rats/dose group) and male and female beagle dogs (1 dog/sex/dose group) given single bolus iv doses or 120-hour continuous iv (civ) infusion doses. For rats given single bolus iv doses of 19.8 or 39.6 mg/m2, mean plasma concentrations of CDDO at 5 minutes after dosing increased proportional to the size of the dose and were 17.9 and 32.7 μM, respectively. CDDO was subsequently eliminated from plasma in two apparent phases with mean half-lives of 0.06 hours (α-phase) and 1.95 hours (β-phase). The total body clearance of CDDO was 9.1 L/m2/hr for rats given 19.8 mg/m2 and 9.5 L/m2/hr for rats given 39.6 mg/m2. The steady state volume of distribution (Vdss) was 13.3 or 15.8 L/m2 for rats given 19.8 or 39.6 mg/m2, respectively. For two dogs administered a single iv bolus dose of 60 mg/m2, CDDO was eliminated from plasma with mean half-lives of 0.02 and 0.65 hours. The mean clearance and steady state volume of distribution of CDDO in these dogs were 44.6 L/m2/hr and 26.8 L/m2, respectively. For rats given 120-hour civ doses of 0, 6, 18, 54, or 108 mg/m2/hr, mortality was observed within 24 hours after the start of the infusion of doses ≥18 mg/m2/hr. Drug-related toxicity included adverse clinical signs (diarrhea, hunched posture, piloerection), body weight loss, clinical pathology changes (including increases in BUN, AST, and ALT, and decreases in ALP), and histopathological changes (including lesions in the liver). No toxicity, as indicated by the absence of adverse clinical signs, changes in body weight, or changes in clinical chemistry parameters, was observed for dogs given 120-hr civ doses of CDDO of 20 or 50 mg/m2/hr. Mean steady state plasma concentrations of CDDO observed during the 120-hr infusion period were 0.886 μuM for dogs given 20 mg/m2/hr and 2.46 μM for dogs given 50 mg/m2/hr. The results of these studies indicated that, at the doses given, CDDO exhibited linear pharmacokinetics in rats and dogs. When given as 120-hr civ infusion doses, the maximum tolerated dose of CDDO was" @default.
- W2339548077 created "2016-06-24" @default.
- W2339548077 creator A5022545001 @default.
- W2339548077 creator A5034690406 @default.
- W2339548077 creator A5058043204 @default.
- W2339548077 creator A5088978867 @default.
- W2339548077 creator A5090366405 @default.
- W2339548077 date "2004-04-01" @default.
- W2339548077 modified "2023-09-24" @default.
- W2339548077 title "Preclinical studies with dihydronaphthalene monophenol (NSC D725087), a vascular targeting agent, and its monophosphate prodrug (NSC D725088)." @default.
- W2339548077 hasPublicationYear "2004" @default.
- W2339548077 type Work @default.
- W2339548077 sameAs 2339548077 @default.
- W2339548077 citedByCount "0" @default.
- W2339548077 crossrefType "journal-article" @default.
- W2339548077 hasAuthorship W2339548077A5022545001 @default.
- W2339548077 hasAuthorship W2339548077A5034690406 @default.
- W2339548077 hasAuthorship W2339548077A5058043204 @default.
- W2339548077 hasAuthorship W2339548077A5088978867 @default.
- W2339548077 hasAuthorship W2339548077A5090366405 @default.
- W2339548077 hasConcept C110121322 @default.
- W2339548077 hasConcept C112705442 @default.
- W2339548077 hasConcept C126322002 @default.
- W2339548077 hasConcept C134018914 @default.
- W2339548077 hasConcept C134306372 @default.
- W2339548077 hasConcept C139254425 @default.
- W2339548077 hasConcept C150903083 @default.
- W2339548077 hasConcept C185592680 @default.
- W2339548077 hasConcept C202751555 @default.
- W2339548077 hasConcept C207001950 @default.
- W2339548077 hasConcept C2776820430 @default.
- W2339548077 hasConcept C3020190219 @default.
- W2339548077 hasConcept C33923547 @default.
- W2339548077 hasConcept C43376680 @default.
- W2339548077 hasConcept C55493867 @default.
- W2339548077 hasConcept C71924100 @default.
- W2339548077 hasConcept C86803240 @default.
- W2339548077 hasConcept C98274493 @default.
- W2339548077 hasConceptScore W2339548077C110121322 @default.
- W2339548077 hasConceptScore W2339548077C112705442 @default.
- W2339548077 hasConceptScore W2339548077C126322002 @default.
- W2339548077 hasConceptScore W2339548077C134018914 @default.
- W2339548077 hasConceptScore W2339548077C134306372 @default.
- W2339548077 hasConceptScore W2339548077C139254425 @default.
- W2339548077 hasConceptScore W2339548077C150903083 @default.
- W2339548077 hasConceptScore W2339548077C185592680 @default.
- W2339548077 hasConceptScore W2339548077C202751555 @default.
- W2339548077 hasConceptScore W2339548077C207001950 @default.
- W2339548077 hasConceptScore W2339548077C2776820430 @default.
- W2339548077 hasConceptScore W2339548077C3020190219 @default.
- W2339548077 hasConceptScore W2339548077C33923547 @default.
- W2339548077 hasConceptScore W2339548077C43376680 @default.
- W2339548077 hasConceptScore W2339548077C55493867 @default.
- W2339548077 hasConceptScore W2339548077C71924100 @default.
- W2339548077 hasConceptScore W2339548077C86803240 @default.
- W2339548077 hasConceptScore W2339548077C98274493 @default.
- W2339548077 hasLocation W23395480771 @default.
- W2339548077 hasOpenAccess W2339548077 @default.
- W2339548077 hasPrimaryLocation W23395480771 @default.
- W2339548077 hasRelatedWork W1443108546 @default.
- W2339548077 hasRelatedWork W1603453470 @default.
- W2339548077 hasRelatedWork W1814583530 @default.
- W2339548077 hasRelatedWork W1967489972 @default.
- W2339548077 hasRelatedWork W1978219119 @default.
- W2339548077 hasRelatedWork W2152362659 @default.
- W2339548077 hasRelatedWork W2257566411 @default.
- W2339548077 hasRelatedWork W2323099604 @default.
- W2339548077 hasRelatedWork W2328569641 @default.
- W2339548077 hasRelatedWork W2357740025 @default.
- W2339548077 hasRelatedWork W2358489756 @default.
- W2339548077 hasRelatedWork W2366793750 @default.
- W2339548077 hasRelatedWork W2398845841 @default.
- W2339548077 hasRelatedWork W2412272173 @default.
- W2339548077 hasRelatedWork W2419265082 @default.
- W2339548077 hasRelatedWork W3096705707 @default.
- W2339548077 hasRelatedWork W1553064761 @default.
- W2339548077 hasRelatedWork W2183042791 @default.
- W2339548077 hasRelatedWork W2805049298 @default.
- W2339548077 hasRelatedWork W2986338185 @default.
- W2339548077 hasVolume "64" @default.
- W2339548077 isParatext "false" @default.
- W2339548077 isRetracted "false" @default.
- W2339548077 magId "2339548077" @default.
- W2339548077 workType "article" @default.