Matches in SemOpenAlex for { <https://semopenalex.org/work/W2069804561> ?p ?o ?g. }
Showing items 1 to 91 of
91
with 100 items per page.
- W2069804561 endingPage "773" @default.
- W2069804561 startingPage "750" @default.
- W2069804561 abstract "The bioavailability, fraction of dose that reaches systemic circulation, of orally administered drugs is often limited by both physical barriers of the intestine (e.g., unstirred-water and mucosal layers, epithelial tight junctions) as well as biochemical barriers such as cytochromes P450 (CYP) and P-glycoprotein (P-gp). Highly expressed in intestine and liver, CYP and P-gp can limit the systemicavailability of parent-drug by metabolism and efflux, respectively, by means of similarly large and flexible active sites that accommodate a variety of structurally-diverse, lipophilic molecules over a wide-range of molecular weights. Consequently, many molecules that are substrates for CYP3A4 also demonstrate affinity for P-gp and numerous studies have reported that for these dual-substrates, CYP3A4 and P-gp afford an interplay that affects bioavailability and clearance in a manner that is non-linear. Several in vitro and in situ models of metabolism and permeability, including transfected cell lines, isolated tissues and perfused organs as well as computational models including physiologically-based pharmacokinetic models of such co-expressing systems have demonstrated this phenomenon of CYP3A/Pgp interplay. Furthermore, recent availability of ligand bound X-ray co-crystal structures of the CYP3A4 and P-gp binding sites coupled with computational docking techniques and other validated in silico models, provide medicinal chemists with tools to inform structuraldesign modifications that can modify the interaction with one or both proteins. This article provides a review of relevant in silico, in vitro, ex vivo and in situ models that allow for investigation of the extent to which clearance or bioavailability can be affected by CYP/P-gp interplay. Keywords: Cytochrome P450, in silico modeling, in vitro models, in situ models, metabolic enzymes, P-glycoprotein, transporters, transporter- enzyme interplay, affinity, substrates" @default.
- W2069804561 created "2016-06-24" @default.
- W2069804561 creator A5023015629 @default.
- W2069804561 creator A5040805324 @default.
- W2069804561 creator A5048587374 @default.
- W2069804561 date "2011-10-01" @default.
- W2069804561 modified "2023-10-14" @default.
- W2069804561 title "In Silico, In Vitro and In Situ Models to Assess Interplay Between CYP3A and P-gp" @default.
- W2069804561 doi "https://doi.org/10.2174/138920011798356999" @default.
- W2069804561 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21568936" @default.
- W2069804561 hasPublicationYear "2011" @default.
- W2069804561 type Work @default.
- W2069804561 sameAs 2069804561 @default.
- W2069804561 citedByCount "29" @default.
- W2069804561 countsByYear W20698045612012 @default.
- W2069804561 countsByYear W20698045612013 @default.
- W2069804561 countsByYear W20698045612014 @default.
- W2069804561 countsByYear W20698045612015 @default.
- W2069804561 countsByYear W20698045612016 @default.
- W2069804561 countsByYear W20698045612017 @default.
- W2069804561 countsByYear W20698045612019 @default.
- W2069804561 countsByYear W20698045612020 @default.
- W2069804561 countsByYear W20698045612022 @default.
- W2069804561 crossrefType "journal-article" @default.
- W2069804561 hasAuthorship W2069804561A5023015629 @default.
- W2069804561 hasAuthorship W2069804561A5040805324 @default.
- W2069804561 hasAuthorship W2069804561A5048587374 @default.
- W2069804561 hasConcept C104317684 @default.
- W2069804561 hasConcept C109650736 @default.
- W2069804561 hasConcept C112705442 @default.
- W2069804561 hasConcept C11824378 @default.
- W2069804561 hasConcept C133936738 @default.
- W2069804561 hasConcept C181389837 @default.
- W2069804561 hasConcept C185592680 @default.
- W2069804561 hasConcept C200082930 @default.
- W2069804561 hasConcept C202751555 @default.
- W2069804561 hasConcept C207001950 @default.
- W2069804561 hasConcept C2775905019 @default.
- W2069804561 hasConcept C2778707650 @default.
- W2069804561 hasConcept C501593827 @default.
- W2069804561 hasConcept C526171541 @default.
- W2069804561 hasConcept C54355233 @default.
- W2069804561 hasConcept C55493867 @default.
- W2069804561 hasConcept C62231903 @default.
- W2069804561 hasConcept C70721500 @default.
- W2069804561 hasConcept C86803240 @default.
- W2069804561 hasConcept C87644729 @default.
- W2069804561 hasConcept C98274493 @default.
- W2069804561 hasConceptScore W2069804561C104317684 @default.
- W2069804561 hasConceptScore W2069804561C109650736 @default.
- W2069804561 hasConceptScore W2069804561C112705442 @default.
- W2069804561 hasConceptScore W2069804561C11824378 @default.
- W2069804561 hasConceptScore W2069804561C133936738 @default.
- W2069804561 hasConceptScore W2069804561C181389837 @default.
- W2069804561 hasConceptScore W2069804561C185592680 @default.
- W2069804561 hasConceptScore W2069804561C200082930 @default.
- W2069804561 hasConceptScore W2069804561C202751555 @default.
- W2069804561 hasConceptScore W2069804561C207001950 @default.
- W2069804561 hasConceptScore W2069804561C2775905019 @default.
- W2069804561 hasConceptScore W2069804561C2778707650 @default.
- W2069804561 hasConceptScore W2069804561C501593827 @default.
- W2069804561 hasConceptScore W2069804561C526171541 @default.
- W2069804561 hasConceptScore W2069804561C54355233 @default.
- W2069804561 hasConceptScore W2069804561C55493867 @default.
- W2069804561 hasConceptScore W2069804561C62231903 @default.
- W2069804561 hasConceptScore W2069804561C70721500 @default.
- W2069804561 hasConceptScore W2069804561C86803240 @default.
- W2069804561 hasConceptScore W2069804561C87644729 @default.
- W2069804561 hasConceptScore W2069804561C98274493 @default.
- W2069804561 hasIssue "8" @default.
- W2069804561 hasLocation W20698045611 @default.
- W2069804561 hasLocation W20698045612 @default.
- W2069804561 hasOpenAccess W2069804561 @default.
- W2069804561 hasPrimaryLocation W20698045611 @default.
- W2069804561 hasRelatedWork W2032914785 @default.
- W2069804561 hasRelatedWork W2129149779 @default.
- W2069804561 hasRelatedWork W2317193739 @default.
- W2069804561 hasRelatedWork W2386015328 @default.
- W2069804561 hasRelatedWork W2605396748 @default.
- W2069804561 hasRelatedWork W2797994387 @default.
- W2069804561 hasRelatedWork W2898078665 @default.
- W2069804561 hasRelatedWork W2966127809 @default.
- W2069804561 hasRelatedWork W2984335229 @default.
- W2069804561 hasRelatedWork W4229457406 @default.
- W2069804561 hasVolume "12" @default.
- W2069804561 isParatext "false" @default.
- W2069804561 isRetracted "false" @default.
- W2069804561 magId "2069804561" @default.
- W2069804561 workType "article" @default.