FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2142309843> ?p ?o ?g. }

• W2142309843 endingPage "8" @default.
• W2142309843 startingPage "1113" @default.
• W2142309843 abstract "L-368,899 is a potent, orally-active oxytocin antagonist that completed phase I clinical trials for the prevention of preterm labor. The pharmacokinetics and disposition of L-368,899 were studied in rats (female and male) and dogs (female), the two species used in the toxicology studies. L-368,899 exhibited similar pharmacokinetics in rats and dogs. After iv dosing at 1, 2.5, and 10 mg/kg, the compound had a t1/2 of approximately 2 hr and plasma clearance between 23 and 36 ml/min/kg at all doses and in both species. The exception was female rats at the 10 mg/kg dose where plasma clearance decreased to 18 ml/min/kg. The Vdss was between 2.0 and 2.6 liters/kg for rats and 3.4 to 4.9 liters/kg for dogs. After oral doing, L-368,899 was rapidly absorbed. Mean Cmax values were achieved at <1 hr at the low doses (25 mg/kg in rats and 5 mg/kg in dogs) and between 1 and 4 hr at the higher doses (100 mg/kg in rats and 33 mg/kg in dogs). In bile duct-cannulated female rats, approximately 70% of a radioactive 28 mg/kg dose was recovered in bile and urine within 72 hr post dose. Plasma drug concentrations were higher in female than in male rats especially at the 25 mg/kg dose, where mean AUC values were 4.5-fold higher in the females. In both rats and dogs, plasma drug levels increased more than proportionally with increasing oral dose. In female rats, the mean AUC increased by approximately 8-fold between 25 and 100 mg/kg, while in female dogs, the mean AUC at the 33 mg/kg dose was 12-fold higher than that at 5 mg/kg. Oral bioavailability was estimated at 14% and 18% for the 5 mg/kg dose in female and male rats, respectively, 41% for the 25 mg/kg dose in male rats and 17% and 41%, respectively, for the 5 and 33 mg/kg doses in dogs. Owing to nonlinear kinetics, bioavailability could not be calculated for the other oral doses. L-368,899 was metabolized extensively in both species after iv and oral dosing, with <10% of the dose excreted unchanged. The main route of elimination was via the feces, which contained >70% of the radioactive dose by 48 hr, primarily as metabolites. The gender and dose dependence of the pharmacokinetics of L-389,899 in rats were attributed to gender differences in metabolizing capacity and saturation of hepatic metabolism, respectively. This conclusion was based primarily on results from experiments comparing the rate of in vitro metabolism of L-368,899 in liver microsomes, which showed that the Vmax and KM values for L-368,899 were 4-fold lower in female than in male rat liver microsomes." @default.
• W2142309843 created "2016-06-24" @default.
• W2142309843 creator A5001097470 @default.
• W2142309843 creator A5005639381 @default.
• W2142309843 creator A5022667104 @default.
• W2142309843 creator A5041110892 @default.
• W2142309843 creator A5053283016 @default.
• W2142309843 creator A5053657853 @default.
• W2142309843 creator A5066405259 @default.
• W2142309843 creator A5067942703 @default.
• W2142309843 date "1997-10-01" @default.
• W2142309843 modified "2023-09-26" @default.
• W2142309843 title "Pharmacokinetics and disposition of the oxytocin receptor antagonist L-368,899 in rats and dogs." @default.
• W2142309843 cites W1966050085 @default.
• W2142309843 cites W1972261909 @default.
• W2142309843 cites W1973461107 @default.
• W2142309843 cites W1981764195 @default.
• W2142309843 cites W1989325575 @default.
• W2142309843 cites W1992208519 @default.
• W2142309843 cites W1993191671 @default.
• W2142309843 cites W2015380892 @default.
• W2142309843 cites W2021648852 @default.
• W2142309843 cites W2022869105 @default.
• W2142309843 cites W2026578696 @default.
• W2142309843 cites W2036520108 @default.
• W2142309843 cites W2047241297 @default.
• W2142309843 cites W2072973977 @default.
• W2142309843 cites W2116898056 @default.
• W2142309843 cites W2136191276 @default.
• W2142309843 cites W2169830226 @default.
• W2142309843 cites W2214818707 @default.
• W2142309843 cites W2499563853 @default.
• W2142309843 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9321512" @default.
• W2142309843 hasPublicationYear "1997" @default.
• W2142309843 type Work @default.
• W2142309843 sameAs 2142309843 @default.
• W2142309843 citedByCount "15" @default.
• W2142309843 countsByYear W21423098432015 @default.
• W2142309843 countsByYear W21423098432016 @default.
• W2142309843 countsByYear W21423098432017 @default.
• W2142309843 countsByYear W21423098432018 @default.
• W2142309843 countsByYear W21423098432019 @default.
• W2142309843 countsByYear W21423098432022 @default.
• W2142309843 crossrefType "journal-article" @default.
• W2142309843 hasAuthorship W2142309843A5001097470 @default.
• W2142309843 hasAuthorship W2142309843A5005639381 @default.
• W2142309843 hasAuthorship W2142309843A5022667104 @default.
• W2142309843 hasAuthorship W2142309843A5041110892 @default.
• W2142309843 hasAuthorship W2142309843A5053283016 @default.
• W2142309843 hasAuthorship W2142309843A5053657853 @default.
• W2142309843 hasAuthorship W2142309843A5066405259 @default.
• W2142309843 hasAuthorship W2142309843A5067942703 @default.
• W2142309843 hasConcept C112705442 @default.
• W2142309843 hasConcept C126322002 @default.
• W2142309843 hasConcept C134018914 @default.
• W2142309843 hasConcept C170493617 @default.
• W2142309843 hasConcept C185592680 @default.
• W2142309843 hasConcept C22979827 @default.
• W2142309843 hasConcept C2776176026 @default.
• W2142309843 hasConcept C2776885963 @default.
• W2142309843 hasConcept C2777056448 @default.
• W2142309843 hasConcept C2777288759 @default.
• W2142309843 hasConcept C2780026642 @default.
• W2142309843 hasConcept C71924100 @default.
• W2142309843 hasConcept C98274493 @default.
• W2142309843 hasConceptScore W2142309843C112705442 @default.
• W2142309843 hasConceptScore W2142309843C126322002 @default.
• W2142309843 hasConceptScore W2142309843C134018914 @default.
• W2142309843 hasConceptScore W2142309843C170493617 @default.
• W2142309843 hasConceptScore W2142309843C185592680 @default.
• W2142309843 hasConceptScore W2142309843C22979827 @default.
• W2142309843 hasConceptScore W2142309843C2776176026 @default.
• W2142309843 hasConceptScore W2142309843C2776885963 @default.
• W2142309843 hasConceptScore W2142309843C2777056448 @default.
• W2142309843 hasConceptScore W2142309843C2777288759 @default.
• W2142309843 hasConceptScore W2142309843C2780026642 @default.
• W2142309843 hasConceptScore W2142309843C71924100 @default.
• W2142309843 hasConceptScore W2142309843C98274493 @default.
• W2142309843 hasIssue "10" @default.
• W2142309843 hasLocation W21423098431 @default.
• W2142309843 hasOpenAccess W2142309843 @default.
• W2142309843 hasPrimaryLocation W21423098431 @default.
• W2142309843 hasRelatedWork W111038150 @default.
• W2142309843 hasRelatedWork W2020497888 @default.
• W2142309843 hasRelatedWork W2064759457 @default.
• W2142309843 hasRelatedWork W2075612064 @default.
• W2142309843 hasRelatedWork W2129532598 @default.
• W2142309843 hasRelatedWork W2145462538 @default.
• W2142309843 hasRelatedWork W2360541311 @default.
• W2142309843 hasRelatedWork W2413529044 @default.
• W2142309843 hasRelatedWork W3210726414 @default.
• W2142309843 hasRelatedWork W4224326956 @default.
• W2142309843 hasVolume "25" @default.
• W2142309843 isParatext "false" @default.
• W2142309843 isRetracted "false" @default.
• W2142309843 magId "2142309843" @default.
• W2142309843 workType "article" @default.