Matches in SemOpenAlex for { <https://semopenalex.org/work/W2131001490> ?p ?o ?g. }
- W2131001490 endingPage "8511" @default.
- W2131001490 startingPage "8503" @default.
- W2131001490 abstract "Abstract Dimethyl benzoylphenylurea (BPU) is a novel tubulin-interactive agent with poor and highly variable oral bioavailability. In a phase I clinical trial of BPU, higher plasma exposure to BPU and metabolites was observed in patients who experienced dose-limiting toxicity. The elucidation of the clinical pharmacology of BPU was sought. BPU, monomethylBPU, and aminoBPU were metabolized by human liver microsomes. Studies with cDNA-expressed human cytochrome P450 enzymes revealed that BPU was metabolized predominantly by CYP3A4 and CYP1A1 but was also a substrate for CYP2C8, CYP2D6, CYP3A5, and CYP3A7. BPU was not a substrate for the efflux transporter ABCG2. Using simultaneous high-performance liquid chromatography/diode array and tandem mass spectrometry detection, we identified six metabolites in human liver microsomes, plasma, or urine: monomethylBPU, aminoBPU, G280, G308, G322, and G373. In patient urine, aminoBPU, G280, G308, and G322 collectively represented <2% of the given BPU dose. G280, G308, G322, and G373 showed minimal cytotoxicity. When BPU was given p.o. to mice in the presence and absence of the CYP3A and ABCG2 inhibitor, ritonavir, there was an increase in BPU plasma exposure and decrease in metabolite exposure but no overall change in cumulative exposure to BPU and the cytotoxic metabolites. Thus, we conclude that (a) CYP3A4 and CYP1A1 are the predominant cytochrome P450 enzymes that catalyze BPU metabolism, (b) BPU is metabolized to two cytotoxic and four noncytotoxic metabolites, and (c) ritonavir inhibits BPU metabolism to improve the systemic exposure to BPU without altering cumulative exposure to BPU and the cytotoxic metabolites." @default.
- W2131001490 created "2016-06-24" @default.
- W2131001490 creator A5007992309 @default.
- W2131001490 creator A5011382691 @default.
- W2131001490 creator A5015341987 @default.
- W2131001490 creator A5018732170 @default.
- W2131001490 creator A5020687338 @default.
- W2131001490 creator A5026024346 @default.
- W2131001490 creator A5047493296 @default.
- W2131001490 creator A5051562975 @default.
- W2131001490 creator A5069613777 @default.
- W2131001490 creator A5070311235 @default.
- W2131001490 creator A5077260725 @default.
- W2131001490 creator A5078259926 @default.
- W2131001490 creator A5086660695 @default.
- W2131001490 date "2005-12-01" @default.
- W2131001490 modified "2023-09-27" @default.
- W2131001490 title "<i>In vitro</i> and <i>In vivo</i> Clinical Pharmacology of Dimethyl Benzoylphenylurea, a Novel Oral Tubulin-Interactive Agent" @default.
- W2131001490 cites W1965478395 @default.
- W2131001490 cites W1969639825 @default.
- W2131001490 cites W1972341029 @default.
- W2131001490 cites W1974447310 @default.
- W2131001490 cites W1996323553 @default.
- W2131001490 cites W2012902529 @default.
- W2131001490 cites W2029789274 @default.
- W2131001490 cites W2032655683 @default.
- W2131001490 cites W2034295073 @default.
- W2131001490 cites W2034659561 @default.
- W2131001490 cites W2038372170 @default.
- W2131001490 cites W2042857186 @default.
- W2131001490 cites W2050767064 @default.
- W2131001490 cites W2077510533 @default.
- W2131001490 cites W2095060296 @default.
- W2131001490 cites W2096956997 @default.
- W2131001490 cites W2102530919 @default.
- W2131001490 cites W2105902511 @default.
- W2131001490 cites W2109689528 @default.
- W2131001490 cites W2114918609 @default.
- W2131001490 cites W2118207487 @default.
- W2131001490 cites W2126820189 @default.
- W2131001490 cites W2130482724 @default.
- W2131001490 cites W2138106072 @default.
- W2131001490 cites W2148146955 @default.
- W2131001490 cites W2323630768 @default.
- W2131001490 cites W2323956706 @default.
- W2131001490 cites W2358501499 @default.
- W2131001490 doi "https://doi.org/10.1158/1078-0432.ccr-05-1037" @default.
- W2131001490 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16322314" @default.
- W2131001490 hasPublicationYear "2005" @default.
- W2131001490 type Work @default.
- W2131001490 sameAs 2131001490 @default.
- W2131001490 citedByCount "10" @default.
- W2131001490 countsByYear W21310014902012 @default.
- W2131001490 countsByYear W21310014902014 @default.
- W2131001490 countsByYear W21310014902015 @default.
- W2131001490 countsByYear W21310014902019 @default.
- W2131001490 countsByYear W21310014902022 @default.
- W2131001490 countsByYear W21310014902023 @default.
- W2131001490 crossrefType "journal-article" @default.
- W2131001490 hasAuthorship W2131001490A5007992309 @default.
- W2131001490 hasAuthorship W2131001490A5011382691 @default.
- W2131001490 hasAuthorship W2131001490A5015341987 @default.
- W2131001490 hasAuthorship W2131001490A5018732170 @default.
- W2131001490 hasAuthorship W2131001490A5020687338 @default.
- W2131001490 hasAuthorship W2131001490A5026024346 @default.
- W2131001490 hasAuthorship W2131001490A5047493296 @default.
- W2131001490 hasAuthorship W2131001490A5051562975 @default.
- W2131001490 hasAuthorship W2131001490A5069613777 @default.
- W2131001490 hasAuthorship W2131001490A5070311235 @default.
- W2131001490 hasAuthorship W2131001490A5077260725 @default.
- W2131001490 hasAuthorship W2131001490A5078259926 @default.
- W2131001490 hasAuthorship W2131001490A5086660695 @default.
- W2131001490 hasConcept C109650736 @default.
- W2131001490 hasConcept C112705442 @default.
- W2131001490 hasConcept C11824378 @default.
- W2131001490 hasConcept C126322002 @default.
- W2131001490 hasConcept C150903083 @default.
- W2131001490 hasConcept C181389837 @default.
- W2131001490 hasConcept C185592680 @default.
- W2131001490 hasConcept C202751555 @default.
- W2131001490 hasConcept C207001950 @default.
- W2131001490 hasConcept C2777477808 @default.
- W2131001490 hasConcept C29730261 @default.
- W2131001490 hasConcept C526171541 @default.
- W2131001490 hasConcept C55493867 @default.
- W2131001490 hasConcept C62231903 @default.
- W2131001490 hasConcept C71924100 @default.
- W2131001490 hasConcept C86803240 @default.
- W2131001490 hasConcept C87644729 @default.
- W2131001490 hasConcept C98274493 @default.
- W2131001490 hasConceptScore W2131001490C109650736 @default.
- W2131001490 hasConceptScore W2131001490C112705442 @default.
- W2131001490 hasConceptScore W2131001490C11824378 @default.
- W2131001490 hasConceptScore W2131001490C126322002 @default.
- W2131001490 hasConceptScore W2131001490C150903083 @default.
- W2131001490 hasConceptScore W2131001490C181389837 @default.
- W2131001490 hasConceptScore W2131001490C185592680 @default.
- W2131001490 hasConceptScore W2131001490C202751555 @default.