FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2155258438> ?p ?o ?g. }

• W2155258438 endingPage "512" @default.
• W2155258438 startingPage "503" @default.
• W2155258438 abstract "Selection of in vitro models that accurately characterize metabolite systemic and hepatobiliary exposure remains a challenge in drug development. In the present study, mechanisms underlying differences in systemic exposure of two active metabolites, furamidine and 2,5-bis (5-amidino)-2-pyridyl furan (CPD-0801), were examined using two hepatic models from rats: isolated perfused livers (IPLs) and sandwich-cultured hepatocytes (SCH). Pafuramidine, a prodrug of furamidine, and 2,5-bis [5-(<i>N</i>-methoxyamidino)-2-pyridyl] furan (CPD-0868), a prodrug of CPD-0801, were selected for investigation because CPD-0801 exhibits greater systemic exposure than furamidine, despite remarkable structural similarity between these two active metabolites. In both IPLs and SCH, the extent of conversion of CPD-0868 to CPD-0801 was consistently higher than that of pafuramidine to furamidine over time (at most 2.5-fold); area under the curve (AUC) of CPD-0801 in IPL perfusate and SCH medium was at least 7-fold higher than that of furamidine. Pharmacokinetic modeling revealed that the rate constant for basolateral (liver to blood) net efflux (<i>k</i>_{A_net efflux}) of total formed CPD-0801 (bound + unbound) was 6-fold higher than that of furamidine. Hepatic accumulation of both active metabolites was extensive (>95% of total formed); the hepatic unbound fraction (<i>f</i>_u,L) of CPD-0801 was 5-fold higher than that of furamidine (1.6 versus 0.3%). Incorporation of <i>f</i>_u,L into the pharmacokinetic model resulted in comparable <i>k</i>_{A_net efflux,u} between furamidine and CPD-0801. In conclusion, intrahepatic binding markedly influenced the disposition of these active metabolites. A higher <i>f</i>_u,L explained, in part, the enhanced perfusate AUC of CPD-0801 compared with furamidine in IPLs. SCH predicted the disposition of prodrug/metabolite in IPLs." @default.
• W2155258438 created "2016-06-24" @default.
• W2155258438 creator A5006973556 @default.
• W2155258438 creator A5049414071 @default.
• W2155258438 creator A5056589677 @default.
• W2155258438 creator A5065639483 @default.
• W2155258438 creator A5076626346 @default.
• W2155258438 creator A5080123057 @default.
• W2155258438 creator A5083433629 @default.
• W2155258438 date "2011-02-14" @default.
• W2155258438 modified "2023-10-03" @default.
• W2155258438 title "Mechanisms Underlying Differences in Systemic Exposure of Structurally Similar Active Metabolites: Comparison of Two Preclinical Hepatic Models" @default.
• W2155258438 cites W1518557248 @default.
• W2155258438 cites W157264296 @default.
• W2155258438 cites W1965613652 @default.
• W2155258438 cites W1986809062 @default.
• W2155258438 cites W1998914143 @default.
• W2155258438 cites W2005678524 @default.
• W2155258438 cites W2011321815 @default.
• W2155258438 cites W2021725670 @default.
• W2155258438 cites W2026253045 @default.
• W2155258438 cites W2027665912 @default.
• W2155258438 cites W2028311915 @default.
• W2155258438 cites W2030404781 @default.
• W2155258438 cites W2035026362 @default.
• W2155258438 cites W2036987218 @default.
• W2155258438 cites W2038014794 @default.
• W2155258438 cites W2042506106 @default.
• W2155258438 cites W2052601882 @default.
• W2155258438 cites W2089338956 @default.
• W2155258438 cites W2101528448 @default.
• W2155258438 cites W2102098329 @default.
• W2155258438 cites W2122738561 @default.
• W2155258438 cites W2123947571 @default.
• W2155258438 cites W2132107140 @default.
• W2155258438 cites W2145481170 @default.
• W2155258438 cites W2162138804 @default.
• W2155258438 cites W2171534546 @default.
• W2155258438 cites W2414945378 @default.
• W2155258438 doi "https://doi.org/10.1124/jpet.110.177220" @default.
• W2155258438 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3083101" @default.
• W2155258438 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21320872" @default.
• W2155258438 hasPublicationYear "2011" @default.
• W2155258438 type Work @default.
• W2155258438 sameAs 2155258438 @default.
• W2155258438 citedByCount "23" @default.
• W2155258438 countsByYear W21552584382012 @default.
• W2155258438 countsByYear W21552584382013 @default.
• W2155258438 countsByYear W21552584382014 @default.
• W2155258438 countsByYear W21552584382015 @default.
• W2155258438 countsByYear W21552584382016 @default.
• W2155258438 countsByYear W21552584382017 @default.
• W2155258438 countsByYear W21552584382018 @default.
• W2155258438 countsByYear W21552584382021 @default.
• W2155258438 crossrefType "journal-article" @default.
• W2155258438 hasAuthorship W2155258438A5006973556 @default.
• W2155258438 hasAuthorship W2155258438A5049414071 @default.
• W2155258438 hasAuthorship W2155258438A5056589677 @default.
• W2155258438 hasAuthorship W2155258438A5065639483 @default.
• W2155258438 hasAuthorship W2155258438A5076626346 @default.
• W2155258438 hasAuthorship W2155258438A5080123057 @default.
• W2155258438 hasAuthorship W2155258438A5083433629 @default.
• W2155258438 hasBestOaLocation W21552584382 @default.
• W2155258438 hasConcept C108215921 @default.
• W2155258438 hasConcept C112705442 @default.
• W2155258438 hasConcept C149151106 @default.
• W2155258438 hasConcept C185592680 @default.
• W2155258438 hasConcept C200082930 @default.
• W2155258438 hasConcept C202751555 @default.
• W2155258438 hasConcept C2777477808 @default.
• W2155258438 hasConcept C2780035454 @default.
• W2155258438 hasConcept C55493867 @default.
• W2155258438 hasConcept C86803240 @default.
• W2155258438 hasConcept C98274493 @default.
• W2155258438 hasConceptScore W2155258438C108215921 @default.
• W2155258438 hasConceptScore W2155258438C112705442 @default.
• W2155258438 hasConceptScore W2155258438C149151106 @default.
• W2155258438 hasConceptScore W2155258438C185592680 @default.
• W2155258438 hasConceptScore W2155258438C200082930 @default.
• W2155258438 hasConceptScore W2155258438C202751555 @default.
• W2155258438 hasConceptScore W2155258438C2777477808 @default.
• W2155258438 hasConceptScore W2155258438C2780035454 @default.
• W2155258438 hasConceptScore W2155258438C55493867 @default.
• W2155258438 hasConceptScore W2155258438C86803240 @default.
• W2155258438 hasConceptScore W2155258438C98274493 @default.
• W2155258438 hasIssue "2" @default.
• W2155258438 hasLocation W21552584381 @default.
• W2155258438 hasLocation W21552584382 @default.
• W2155258438 hasLocation W21552584383 @default.
• W2155258438 hasLocation W21552584384 @default.
• W2155258438 hasLocation W21552584385 @default.
• W2155258438 hasOpenAccess W2155258438 @default.
• W2155258438 hasPrimaryLocation W21552584381 @default.
• W2155258438 hasRelatedWork W1848347670 @default.
• W2155258438 hasRelatedWork W1964759623 @default.
• W2155258438 hasRelatedWork W2007079254 @default.
• W2155258438 hasRelatedWork W2056938528 @default.
• W2155258438 hasRelatedWork W2081460129 @default.

• next