FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2107567029> ?p ?o ?g. }

• W2107567029 endingPage "502" @default.
• W2107567029 startingPage "491" @default.
• W2107567029 abstract "Objective To determine in humans the relative roles of intestinal and hepatic metabolism in the oral first-pass elimination of a CYP3A substrate using midazolam as a model compound. Methods Midazolam was administered intravenously (1 mg) or orally (2 mg) to 20 healthy young subjects (10 men and 10 women) in a random fashion, and the disposition of the drug and its 1′-hydroxy metabolite were determined. In separate in vitro studies, the CYP3A-mediated formation of 1′-hydroxymidazolam by human hepatic and intestinal microsomes was investigated. Results No gender-related differences were noted in either the systemic (370 ± 114 ml/min [mean ± SD]) or oral (1413 ± 807 ml/min) clearance values of midazolam. Despite complete oral absorption, measured oral bioavailability was on average about 50% less than that predicted on the assumption that only the liver contributed to first-pass metabolism. Pharmacokinetic estimation of the intestinal component indicated an extraction ratio (0.43 ± 0.24) that was similar to that of the liver (0.44 ± 0.14). 1′-Hydroxymidazolam was extensively but variably formed in vitro by both hepatic and intestinal microsomes and, although the intrinsic clearance (Vmax/Km) was higher in the liver (540 ± 747 versus 135 ± 92 μl/min/mg protein), this difference was not statistically significant. Conclusions These results show that the small intestine can be a major site for presystemic, CYP3A-mediated metabolism after oral administration. Moreover, it appears that this represents a true first-pass effect. In addition, intestinal and hepatic metabolism may be important factors in interindividual variability in disposition after oral administration of midazolam and similar CYP3A substrates. Finally, intestinal localization of CYP3A may be significant in metabolism-based drug-drug interactions. Clinical Pharmacology & Therapeutics (1996) 59, 491–502; doi:" @default.
• W2107567029 created "2016-06-24" @default.
• W2107567029 creator A5003659536 @default.
• W2107567029 creator A5004489015 @default.
• W2107567029 creator A5010011309 @default.
• W2107567029 creator A5020683659 @default.
• W2107567029 creator A5050910389 @default.
• W2107567029 creator A5068941997 @default.
• W2107567029 creator A5083433629 @default.
• W2107567029 date "1996-05-01" @default.
• W2107567029 modified "2023-10-02" @default.
• W2107567029 title "Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism*" @default.
• W2107567029 cites W1520965071 @default.
• W2107567029 cites W1775749144 @default.
• W2107567029 cites W1970059344 @default.
• W2107567029 cites W1972280475 @default.
• W2107567029 cites W1978470492 @default.
• W2107567029 cites W1979732900 @default.
• W2107567029 cites W1985984753 @default.
• W2107567029 cites W2002044083 @default.
• W2107567029 cites W2009170744 @default.
• W2107567029 cites W2012293219 @default.
• W2107567029 cites W2015809217 @default.
• W2107567029 cites W2024587809 @default.
• W2107567029 cites W2029627662 @default.
• W2107567029 cites W2030488800 @default.
• W2107567029 cites W2031971349 @default.
• W2107567029 cites W2033033710 @default.
• W2107567029 cites W2054040800 @default.
• W2107567029 cites W2059588998 @default.
• W2107567029 cites W2061407065 @default.
• W2107567029 cites W2070847795 @default.
• W2107567029 cites W2073965718 @default.
• W2107567029 cites W2084376388 @default.
• W2107567029 cites W2104093795 @default.
• W2107567029 cites W399516315 @default.
• W2107567029 cites W4241401467 @default.
• W2107567029 doi "https://doi.org/10.1016/s0009-9236(96)90177-0" @default.
• W2107567029 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8646820" @default.
• W2107567029 hasPublicationYear "1996" @default.
• W2107567029 type Work @default.
• W2107567029 sameAs 2107567029 @default.
• W2107567029 citedByCount "562" @default.
• W2107567029 countsByYear W21075670292012 @default.
• W2107567029 countsByYear W21075670292013 @default.
• W2107567029 countsByYear W21075670292014 @default.
• W2107567029 countsByYear W21075670292015 @default.
• W2107567029 countsByYear W21075670292016 @default.
• W2107567029 countsByYear W21075670292017 @default.
• W2107567029 countsByYear W21075670292018 @default.
• W2107567029 countsByYear W21075670292019 @default.
• W2107567029 countsByYear W21075670292020 @default.
• W2107567029 countsByYear W21075670292021 @default.
• W2107567029 countsByYear W21075670292022 @default.
• W2107567029 countsByYear W21075670292023 @default.
• W2107567029 crossrefType "journal-article" @default.
• W2107567029 hasAuthorship W2107567029A5003659536 @default.
• W2107567029 hasAuthorship W2107567029A5004489015 @default.
• W2107567029 hasAuthorship W2107567029A5010011309 @default.
• W2107567029 hasAuthorship W2107567029A5020683659 @default.
• W2107567029 hasAuthorship W2107567029A5050910389 @default.
• W2107567029 hasAuthorship W2107567029A5068941997 @default.
• W2107567029 hasAuthorship W2107567029A5083433629 @default.
• W2107567029 hasConcept C112705442 @default.
• W2107567029 hasConcept C11824378 @default.
• W2107567029 hasConcept C121332964 @default.
• W2107567029 hasConcept C125287762 @default.
• W2107567029 hasConcept C126322002 @default.
• W2107567029 hasConcept C134018914 @default.
• W2107567029 hasConcept C150903083 @default.
• W2107567029 hasConcept C181389837 @default.
• W2107567029 hasConcept C185592680 @default.
• W2107567029 hasConcept C201253974 @default.
• W2107567029 hasConcept C202751555 @default.
• W2107567029 hasConcept C204810001 @default.
• W2107567029 hasConcept C207001950 @default.
• W2107567029 hasConcept C24890656 @default.
• W2107567029 hasConcept C2776814716 @default.
• W2107567029 hasConcept C2777056448 @default.
• W2107567029 hasConcept C2777477808 @default.
• W2107567029 hasConcept C2777882243 @default.
• W2107567029 hasConcept C2778000748 @default.
• W2107567029 hasConcept C43617362 @default.
• W2107567029 hasConcept C4725764 @default.
• W2107567029 hasConcept C55493867 @default.
• W2107567029 hasConcept C62231903 @default.
• W2107567029 hasConcept C71924100 @default.
• W2107567029 hasConcept C86803240 @default.
• W2107567029 hasConcept C87644729 @default.
• W2107567029 hasConcept C89311334 @default.
• W2107567029 hasConcept C98274493 @default.
• W2107567029 hasConceptScore W2107567029C112705442 @default.
• W2107567029 hasConceptScore W2107567029C11824378 @default.
• W2107567029 hasConceptScore W2107567029C121332964 @default.
• W2107567029 hasConceptScore W2107567029C125287762 @default.
• W2107567029 hasConceptScore W2107567029C126322002 @default.
• W2107567029 hasConceptScore W2107567029C134018914 @default.
• W2107567029 hasConceptScore W2107567029C150903083 @default.

• next