FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4281287810> ?p ?o ?g. }

• W4281287810 abstract "Fenfluramine (FFA) has potent antiseizure activity in severe, pharmacoresistant childhood-onset developmental and epileptic encephalopathies (e.g., Dravet syndrome). To assess risk of drug interaction affecting pharmacokinetics of FFA and its major metabolite, norfenfluramine (nFFA), we conducted in vitro metabolite characterization, reaction phenotyping, and drug transporter-mediated cellular uptake studies. FFA showed low in vitro clearance in human liver S9 fractions and in intestinal S9 fractions in all three species tested (t1/2 > 120 min). Two metabolites (nFFA and an N-oxide or a hydroxylamine) were detected in human liver microsomes versus six in dog and seven in rat liver microsomes; no metabolite was unique to humans. Selective CYP inhibitor studies showed FFA metabolism partially inhibited by quinidine (CYP2D6, 48%), phencyclidine (CYP2B6, 42%), and furafylline (CYP1A2, 32%) and, to a lesser extent (<15%), by tienilic acid (CYP2C9), esomeprazole (CYP2C19), and troleandomycin (CYP3A4/5). Incubation of nFFA with rCYP1A2, rCYP2B6, rCYP2C19, and rCYP2D6 resulted in 10%-20% metabolism and no clear inhibition of nFFA metabolism by any CYP-selective inhibitor. Reaction phenotyping showed metabolism of FFA by recombinant human cytochrome P450 (rCYP) enzymes rCYP2B6 (10%-21% disappearance for 1 and 10 µM FFA, respectively), rCYP1A2 (22%-23%), rCYP2C19 (49%-50%), and rCYP2D6 (59%-97%). Neither FFA nor nFFA was a drug transporter substrate. Results show FFA metabolism to nFFA occurs through multiple pathways of elimination. FFA dose adjustments may be needed when administered with strong inhibitors or inducers of multiple enzymes involved in FFA metabolism (e.g., stiripentol)." @default.
• W4281287810 created "2022-05-24" @default.
• W4281287810 creator A5001772863 @default.
• W4281287810 creator A5015735300 @default.
• W4281287810 creator A5024312890 @default.
• W4281287810 creator A5044894386 @default.
• W4281287810 creator A5049662140 @default.
• W4281287810 creator A5057012991 @default.
• W4281287810 creator A5084547627 @default.
• W4281287810 date "2022-05-22" @default.
• W4281287810 modified "2023-10-01" @default.
• W4281287810 title "In vitro evaluation of fenfluramine and norfenfluramine as victims of drug interactions" @default.
• W4281287810 cites W1413196089 @default.
• W4281287810 cites W1984574841 @default.
• W4281287810 cites W1993199803 @default.
• W4281287810 cites W2006261011 @default.
• W4281287810 cites W2015143190 @default.
• W4281287810 cites W2036208520 @default.
• W4281287810 cites W2044422577 @default.
• W4281287810 cites W2053952400 @default.
• W4281287810 cites W2056150647 @default.
• W4281287810 cites W2063696295 @default.
• W4281287810 cites W2068150904 @default.
• W4281287810 cites W2076215181 @default.
• W4281287810 cites W2079197876 @default.
• W4281287810 cites W2079476893 @default.
• W4281287810 cites W2096565553 @default.
• W4281287810 cites W2102417187 @default.
• W4281287810 cites W2108982217 @default.
• W4281287810 cites W2112546684 @default.
• W4281287810 cites W2129233012 @default.
• W4281287810 cites W2139998690 @default.
• W4281287810 cites W2143689651 @default.
• W4281287810 cites W2152964734 @default.
• W4281287810 cites W2160234096 @default.
• W4281287810 cites W2242706280 @default.
• W4281287810 cites W2295253819 @default.
• W4281287810 cites W2333978873 @default.
• W4281287810 cites W2380610527 @default.
• W4281287810 cites W2465608098 @default.
• W4281287810 cites W2472543315 @default.
• W4281287810 cites W2604363982 @default.
• W4281287810 cites W2771328536 @default.
• W4281287810 cites W2846779511 @default.
• W4281287810 cites W2889968052 @default.
• W4281287810 cites W2897171837 @default.
• W4281287810 cites W2996672198 @default.
• W4281287810 cites W3027196979 @default.
• W4281287810 cites W3162981102 @default.
• W4281287810 cites W3199635621 @default.
• W4281287810 cites W3199710005 @default.
• W4281287810 cites W3201244536 @default.
• W4281287810 cites W4248544072 @default.
• W4281287810 cites W4281286144 @default.
• W4281287810 cites W4281287810 @default.
• W4281287810 doi "https://doi.org/10.1002/prp2.958" @default.
• W4281287810 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35599345" @default.
• W4281287810 hasPublicationYear "2022" @default.
• W4281287810 type Work @default.
• W4281287810 citedByCount "5" @default.
• W4281287810 countsByYear W42812878102022 @default.
• W4281287810 countsByYear W42812878102023 @default.
• W4281287810 crossrefType "journal-article" @default.
• W4281287810 hasAuthorship W4281287810A5001772863 @default.
• W4281287810 hasAuthorship W4281287810A5015735300 @default.
• W4281287810 hasAuthorship W4281287810A5024312890 @default.
• W4281287810 hasAuthorship W4281287810A5044894386 @default.
• W4281287810 hasAuthorship W4281287810A5049662140 @default.
• W4281287810 hasAuthorship W4281287810A5057012991 @default.
• W4281287810 hasAuthorship W4281287810A5084547627 @default.
• W4281287810 hasBestOaLocation W42812878102 @default.
• W4281287810 hasConcept C109650736 @default.
• W4281287810 hasConcept C115368759 @default.
• W4281287810 hasConcept C185592680 @default.
• W4281287810 hasConcept C202751555 @default.
• W4281287810 hasConcept C2777477808 @default.
• W4281287810 hasConcept C2779907587 @default.
• W4281287810 hasConcept C33664856 @default.
• W4281287810 hasConcept C526171541 @default.
• W4281287810 hasConcept C55493867 @default.
• W4281287810 hasConcept C62231903 @default.
• W4281287810 hasConcept C86745063 @default.
• W4281287810 hasConcept C86803240 @default.
• W4281287810 hasConcept C87644729 @default.
• W4281287810 hasConcept C89311334 @default.
• W4281287810 hasConcept C98274493 @default.
• W4281287810 hasConceptScore W4281287810C109650736 @default.
• W4281287810 hasConceptScore W4281287810C115368759 @default.
• W4281287810 hasConceptScore W4281287810C185592680 @default.
• W4281287810 hasConceptScore W4281287810C202751555 @default.
• W4281287810 hasConceptScore W4281287810C2777477808 @default.
• W4281287810 hasConceptScore W4281287810C2779907587 @default.
• W4281287810 hasConceptScore W4281287810C33664856 @default.
• W4281287810 hasConceptScore W4281287810C526171541 @default.
• W4281287810 hasConceptScore W4281287810C55493867 @default.
• W4281287810 hasConceptScore W4281287810C62231903 @default.
• W4281287810 hasConceptScore W4281287810C86745063 @default.
• W4281287810 hasConceptScore W4281287810C86803240 @default.
• W4281287810 hasConceptScore W4281287810C87644729 @default.
• W4281287810 hasConceptScore W4281287810C89311334 @default.

• next