FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1967456965> ?p ?o ?g. }

• W1967456965 endingPage "490" @default.
• W1967456965 startingPage "482" @default.
• W1967456965 abstract "1. To explain the large differences in (the stereoselectivity of) the clearances of the enantiomers of warfarin and acenocoumarol (4'-nitrowarfarin) their human liver microsomal metabolism has been studied and enzyme kinetic parameters determined. The effects of cimetidine, propafenone, sulphaphenazole, and omeprazole on their metabolism has been investigated. 2. The 4-hydroxycoumarins follow similar metabolic routes and are mainly hydroxylated at the 6- and 7-position (accounting for 63 to 99% of the metabolic clearances). 3. Due to the lower Km values of R- and S-acenocoumarol and higher Vmax values of S-acenocoumarol, the overall metabolic clearances of R/S acenocoumarol exceed those of R/S warfarin 6 and 66 times respectively. 4. The metabolism of both compounds is stereoselective for the S-enantiomers, which is 10 times more pronounced in the case of acenocoumarol. 5. Except for the 7-hydroxylation of the R-enantiomers (r = 0.90; P < 0.025), the 6- and 7-hydroxylation rates of R/S warfarin do not correlate with those of R/S acenocoumarol. 6. Sulphaphenazole competitively inhibits the 7- and in some samples partly (up to 50%) the 6-hydroxylation of S-warfarin as well as the 7-hydroxylation of R- and S-acenocoumarol and the 6-hydroxylation of S-acenocoumarol (Kis ranging from 0.5-1.3 microM). 7. Omeprazole partly (40-80%) inhibits the 6- and 7-hydroxylation of R-warfarin (Ki = 99 and 117 microM) and of R- (Ki = 219 and 7.2 microM) and S-acenocoumarol (Ki = 6.1 and 7.7 microM) but not S-warfarin in a competitive manner. 8. Differences in the partial (up to 40%) inhibition of the metabolism of the enantiomers of the 4-hydroxycoumarins were also observed for the relatively weak inhibitors, propafenone and cimetidine.9. The results suggest that the coumarin ring hydroxylations of both compounds are catalysed by different combinations of P450 isozymes. The 7-hydroxylation of R/S acenocoumarol and the 6-hydroxylation of S-acenocoumarol are at least partly conducted by (a) P450 isozyme(s) of the 2C subfamily different from P450 2C9 (the main S-warfarin 7- and 6-hydroxylase)." @default.
• W1967456965 created "2016-06-24" @default.
• W1967456965 creator A5006512815 @default.
• W1967456965 creator A5011767486 @default.
• W1967456965 date "1993-09-01" @default.
• W1967456965 modified "2023-10-17" @default.
• W1967456965 title "Human liver microsomal metabolism of the enantiomers of warfarin and acenocoumarol: P450 isozyme diversity determines the differences in their pharmacokinetics" @default.
• W1967456965 cites W1557943810 @default.
• W1967456965 cites W1775749144 @default.
• W1967456965 cites W1817011321 @default.
• W1967456965 cites W1820017190 @default.
• W1967456965 cites W1900740515 @default.
• W1967456965 cites W1927995536 @default.
• W1967456965 cites W1949792042 @default.
• W1967456965 cites W1968892100 @default.
• W1967456965 cites W1972053711 @default.
• W1967456965 cites W1975566302 @default.
• W1967456965 cites W1978313703 @default.
• W1967456965 cites W1989890429 @default.
• W1967456965 cites W1992111447 @default.
• W1967456965 cites W2001523104 @default.
• W1967456965 cites W2002720546 @default.
• W1967456965 cites W2009340266 @default.
• W1967456965 cites W2017494635 @default.
• W1967456965 cites W2020016242 @default.
• W1967456965 cites W2034602335 @default.
• W1967456965 cites W2036501695 @default.
• W1967456965 cites W2051288524 @default.
• W1967456965 cites W2065976317 @default.
• W1967456965 cites W2075349988 @default.
• W1967456965 cites W2078732261 @default.
• W1967456965 cites W2079368823 @default.
• W1967456965 cites W2084334012 @default.
• W1967456965 cites W2092116907 @default.
• W1967456965 cites W2092191147 @default.
• W1967456965 cites W2109448546 @default.
• W1967456965 cites W2115717824 @default.
• W1967456965 cites W2128818892 @default.
• W1967456965 cites W2139508000 @default.
• W1967456965 cites W2149415752 @default.
• W1967456965 cites W2403381243 @default.
• W1967456965 cites W2410499541 @default.
• W1967456965 cites W2417076726 @default.
• W1967456965 cites W3058535 @default.
• W1967456965 cites W4211044621 @default.
• W1967456965 cites W79171739 @default.
• W1967456965 doi "https://doi.org/10.1111/j.1476-5381.1993.tb13836.x" @default.
• W1967456965 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2175972" @default.
• W1967456965 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8220911" @default.
• W1967456965 hasPublicationYear "1993" @default.
• W1967456965 type Work @default.
• W1967456965 sameAs 1967456965 @default.
• W1967456965 citedByCount "81" @default.
• W1967456965 countsByYear W19674569652012 @default.
• W1967456965 countsByYear W19674569652013 @default.
• W1967456965 countsByYear W19674569652015 @default.
• W1967456965 countsByYear W19674569652016 @default.
• W1967456965 countsByYear W19674569652017 @default.
• W1967456965 countsByYear W19674569652018 @default.
• W1967456965 countsByYear W19674569652019 @default.
• W1967456965 crossrefType "journal-article" @default.
• W1967456965 hasAuthorship W1967456965A5006512815 @default.
• W1967456965 hasAuthorship W1967456965A5011767486 @default.
• W1967456965 hasBestOaLocation W19674569651 @default.
• W1967456965 hasConcept C112705442 @default.
• W1967456965 hasConcept C126322002 @default.
• W1967456965 hasConcept C181199279 @default.
• W1967456965 hasConcept C185592680 @default.
• W1967456965 hasConcept C2776301958 @default.
• W1967456965 hasConcept C2779161974 @default.
• W1967456965 hasConcept C2779907587 @default.
• W1967456965 hasConcept C2781109383 @default.
• W1967456965 hasConcept C2781344064 @default.
• W1967456965 hasConcept C3946865 @default.
• W1967456965 hasConcept C486523 @default.
• W1967456965 hasConcept C526171541 @default.
• W1967456965 hasConcept C55493867 @default.
• W1967456965 hasConcept C62231903 @default.
• W1967456965 hasConcept C71240020 @default.
• W1967456965 hasConcept C71924100 @default.
• W1967456965 hasConcept C86803240 @default.
• W1967456965 hasConcept C87644729 @default.
• W1967456965 hasConcept C98274493 @default.
• W1967456965 hasConceptScore W1967456965C112705442 @default.
• W1967456965 hasConceptScore W1967456965C126322002 @default.
• W1967456965 hasConceptScore W1967456965C181199279 @default.
• W1967456965 hasConceptScore W1967456965C185592680 @default.
• W1967456965 hasConceptScore W1967456965C2776301958 @default.
• W1967456965 hasConceptScore W1967456965C2779161974 @default.
• W1967456965 hasConceptScore W1967456965C2779907587 @default.
• W1967456965 hasConceptScore W1967456965C2781109383 @default.
• W1967456965 hasConceptScore W1967456965C2781344064 @default.
• W1967456965 hasConceptScore W1967456965C3946865 @default.
• W1967456965 hasConceptScore W1967456965C486523 @default.
• W1967456965 hasConceptScore W1967456965C526171541 @default.
• W1967456965 hasConceptScore W1967456965C55493867 @default.
• W1967456965 hasConceptScore W1967456965C62231903 @default.
• W1967456965 hasConceptScore W1967456965C71240020 @default.

• next