FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1987804903> ?p ?o ?g. }

• W1987804903 endingPage "1332" @default.
• W1987804903 startingPage "1325" @default.
• W1987804903 abstract "The hepatic uptake of quinine, fluvoxamine, and fluoxetine (0.1-10 microM) was investigated with freshly isolated rat hepatocytes. The cell-to-medium concentration ratios (K(p)) were concentration-dependent: the mean maximum K(p) values (at 0.1 microM) were 150 (quinine), 500 (fluvoxamine), and 2000 (fluoxetine). There was also a large capacity site that was not saturable over the concentration range used (possibly partition into the phospholipid component of membranes); representing this site, the mean minimum K(p) values (at 10 microM) were 30 (quinine), 200 (fluvoxamine), and 500 (fluoxetine). To eliminate concomitant metabolism, cells were pretreated with the irreversible P450 inhibitor, aminobenzotriazole. The saturable uptake was substantially eliminated after exposure to carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (ATP inhibitor). The difference between the maximum and minimum K(p) for these three amine drugs, as well as for dextromethorphan, propranolol, and imipramine, was within a limited range of 3-fold, indicating a common magnitude of saturable uptake. Basic, permeable drugs are expected to be sequestered into lysosomes, which actively maintain their low internal pH (approximately 5) using ATP, and this process is predictable from the combined effects of pH-driven ion accumulation and unsaturable binding representing partition into membranes. The resultant predicted maximum K(p) correlated strongly with the observed maximum K(p). Thus, at low substrate concentrations, the fraction of drug unbound in the hepatocyte incubation (critical for assessing drug clearance and drug-drug interaction potential) may be dependent upon saturable as well as unsaturable binding, and for lipophilic, basic drugs, this can be readily estimated assuming a common degree of uptake into lysosomes." @default.
• W1987804903 created "2016-06-24" @default.
• W1987804903 creator A5020318922 @default.
• W1987804903 creator A5063870746 @default.
• W1987804903 date "2007-04-30" @default.
• W1987804903 modified "2023-10-16" @default.
• W1987804903 title "Saturable Uptake of Lipophilic Amine Drugs into Isolated Hepatocytes: Mechanisms and Consequences for Quantitative Clearance Prediction" @default.
• W1987804903 cites W110436513 @default.
• W1987804903 cites W1502459074 @default.
• W1987804903 cites W1775749144 @default.
• W1987804903 cites W1952755792 @default.
• W1987804903 cites W1983986879 @default.
• W1987804903 cites W1987020046 @default.
• W1987804903 cites W1991359947 @default.
• W1987804903 cites W2005866145 @default.
• W1987804903 cites W2010241890 @default.
• W1987804903 cites W2024930127 @default.
• W1987804903 cites W2029745021 @default.
• W1987804903 cites W2032390387 @default.
• W1987804903 cites W2037722413 @default.
• W1987804903 cites W2060992818 @default.
• W1987804903 cites W2062237476 @default.
• W1987804903 cites W2063395607 @default.
• W1987804903 cites W2072482644 @default.
• W1987804903 cites W2083878214 @default.
• W1987804903 cites W2091892461 @default.
• W1987804903 cites W2093020551 @default.
• W1987804903 cites W2097322989 @default.
• W1987804903 cites W2098154721 @default.
• W1987804903 cites W2104075487 @default.
• W1987804903 cites W2116796907 @default.
• W1987804903 cites W2117338538 @default.
• W1987804903 cites W2131182345 @default.
• W1987804903 cites W2135176494 @default.
• W1987804903 cites W2137442330 @default.
• W1987804903 cites W2144678297 @default.
• W1987804903 cites W2145123754 @default.
• W1987804903 cites W2145804243 @default.
• W1987804903 cites W2158561731 @default.
• W1987804903 cites W2165334931 @default.
• W1987804903 cites W2338294989 @default.
• W1987804903 cites W4252282252 @default.
• W1987804903 cites W4253344482 @default.
• W1987804903 doi "https://doi.org/10.1124/dmd.107.015131" @default.
• W1987804903 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17470525" @default.
• W1987804903 hasPublicationYear "2007" @default.
• W1987804903 type Work @default.
• W1987804903 sameAs 1987804903 @default.
• W1987804903 citedByCount "65" @default.
• W1987804903 countsByYear W19878049032012 @default.
• W1987804903 countsByYear W19878049032013 @default.
• W1987804903 countsByYear W19878049032014 @default.
• W1987804903 countsByYear W19878049032015 @default.
• W1987804903 countsByYear W19878049032016 @default.
• W1987804903 countsByYear W19878049032017 @default.
• W1987804903 countsByYear W19878049032020 @default.
• W1987804903 countsByYear W19878049032021 @default.
• W1987804903 countsByYear W19878049032022 @default.
• W1987804903 countsByYear W19878049032023 @default.
• W1987804903 crossrefType "journal-article" @default.
• W1987804903 hasAuthorship W1987804903A5020318922 @default.
• W1987804903 hasAuthorship W1987804903A5063870746 @default.
• W1987804903 hasConcept C142724271 @default.
• W1987804903 hasConcept C150757390 @default.
• W1987804903 hasConcept C181199279 @default.
• W1987804903 hasConcept C185592680 @default.
• W1987804903 hasConcept C202751555 @default.
• W1987804903 hasConcept C204787440 @default.
• W1987804903 hasConcept C2776200302 @default.
• W1987804903 hasConcept C2778918659 @default.
• W1987804903 hasConcept C2779145073 @default.
• W1987804903 hasConcept C2779934242 @default.
• W1987804903 hasConcept C41625074 @default.
• W1987804903 hasConcept C55493867 @default.
• W1987804903 hasConcept C71924100 @default.
• W1987804903 hasConcept C86803240 @default.
• W1987804903 hasConcept C98274493 @default.
• W1987804903 hasConceptScore W1987804903C142724271 @default.
• W1987804903 hasConceptScore W1987804903C150757390 @default.
• W1987804903 hasConceptScore W1987804903C181199279 @default.
• W1987804903 hasConceptScore W1987804903C185592680 @default.
• W1987804903 hasConceptScore W1987804903C202751555 @default.
• W1987804903 hasConceptScore W1987804903C204787440 @default.
• W1987804903 hasConceptScore W1987804903C2776200302 @default.
• W1987804903 hasConceptScore W1987804903C2778918659 @default.
• W1987804903 hasConceptScore W1987804903C2779145073 @default.
• W1987804903 hasConceptScore W1987804903C2779934242 @default.
• W1987804903 hasConceptScore W1987804903C41625074 @default.
• W1987804903 hasConceptScore W1987804903C55493867 @default.
• W1987804903 hasConceptScore W1987804903C71924100 @default.
• W1987804903 hasConceptScore W1987804903C86803240 @default.
• W1987804903 hasConceptScore W1987804903C98274493 @default.
• W1987804903 hasIssue "8" @default.
• W1987804903 hasLocation W19878049031 @default.
• W1987804903 hasLocation W19878049032 @default.
• W1987804903 hasOpenAccess W1987804903 @default.
• W1987804903 hasPrimaryLocation W19878049031 @default.
• W1987804903 hasRelatedWork W1973129042 @default.

• next