Matches in SemOpenAlex for { <https://semopenalex.org/work/W2884203481> ?p ?o ?g. }
Showing items 1 to 94 of
94
with 100 items per page.
- W2884203481 endingPage "161" @default.
- W2884203481 startingPage "154" @default.
- W2884203481 abstract "Translation across species and from in vitro to in vivo is a central tenet in drug discovery pharmacology. Successful implementation requires proper assessment of both in vivo potency and efficacy. This notwithstanding, in vivo data is typically defined mostly in terms of ligand-to-target binding affinity, similar to in vitro studies. As in vivo potency and efficacy involve a combination not only of drug, but also partitioning, target, and drug-target-complex events and processes, ignoring some of the central differences between in vivo and in vitro may result in serious miscalculations of in vivo efficacious exposure for translational predictions. We compare potency measures derived from two basic pharmacodynamic model situations: A ‘closed’ in vitro system defining target binding of a ligand when both concentrations remain essentially static, and an ‘open’ in vivo system where target turnover dynamics and elimination of the drug-target complex are also included. Corresponding equilibrium (steady-state) expressions in the central pharmacokinetic compartment are derived and presented. Three representative variants of ‘open’ in vivo systems are discussed, showing relationships for ligand-target complex and ligand for each of the systems and graphically illustrating corresponding shapes. The examples include i) two ligands competing for one target, ii) two targets competing for one ligand (/drug), and iii) target-ligand (/drug) interactions in a peripheral PK compartment. The expanded in vivo potency EC50 expression emphasises the contribution from target-related biology parameters that need accounting for, and particularly that ‘closed’ system (in vitro) properties should not be first choice when ranking compounds in vivo (‘open’ system)." @default.
- W2884203481 created "2018-08-03" @default.
- W2884203481 creator A5002803176 @default.
- W2884203481 creator A5010748930 @default.
- W2884203481 creator A5042682167 @default.
- W2884203481 date "2018-09-01" @default.
- W2884203481 modified "2023-09-25" @default.
- W2884203481 title "Lost in translation: What's in an EC? Innovative PK/PD reasoning in the drug development context" @default.
- W2884203481 cites W151483314 @default.
- W2884203481 cites W1983632874 @default.
- W2884203481 cites W2004084174 @default.
- W2884203481 cites W2004465314 @default.
- W2884203481 cites W2025475039 @default.
- W2884203481 cites W2042099048 @default.
- W2884203481 cites W2044265850 @default.
- W2884203481 cites W2097892506 @default.
- W2884203481 cites W2099297532 @default.
- W2884203481 cites W2117381705 @default.
- W2884203481 cites W2408926036 @default.
- W2884203481 cites W2761250579 @default.
- W2884203481 cites W2790277305 @default.
- W2884203481 cites W2803158279 @default.
- W2884203481 cites W1888980123 @default.
- W2884203481 doi "https://doi.org/10.1016/j.ejphar.2018.07.037" @default.
- W2884203481 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30036536" @default.
- W2884203481 hasPublicationYear "2018" @default.
- W2884203481 type Work @default.
- W2884203481 sameAs 2884203481 @default.
- W2884203481 citedByCount "9" @default.
- W2884203481 countsByYear W28842034812019 @default.
- W2884203481 countsByYear W28842034812021 @default.
- W2884203481 countsByYear W28842034812022 @default.
- W2884203481 countsByYear W28842034812023 @default.
- W2884203481 crossrefType "journal-article" @default.
- W2884203481 hasAuthorship W2884203481A5002803176 @default.
- W2884203481 hasAuthorship W2884203481A5010748930 @default.
- W2884203481 hasAuthorship W2884203481A5042682167 @default.
- W2884203481 hasConcept C111113717 @default.
- W2884203481 hasConcept C112705442 @default.
- W2884203481 hasConcept C116569031 @default.
- W2884203481 hasConcept C151730666 @default.
- W2884203481 hasConcept C170493617 @default.
- W2884203481 hasConcept C185592680 @default.
- W2884203481 hasConcept C202751555 @default.
- W2884203481 hasConcept C207001950 @default.
- W2884203481 hasConcept C2779343474 @default.
- W2884203481 hasConcept C2780035454 @default.
- W2884203481 hasConcept C54355233 @default.
- W2884203481 hasConcept C55493867 @default.
- W2884203481 hasConcept C57992300 @default.
- W2884203481 hasConcept C64903051 @default.
- W2884203481 hasConcept C70721500 @default.
- W2884203481 hasConcept C74187038 @default.
- W2884203481 hasConcept C86803240 @default.
- W2884203481 hasConcept C98274493 @default.
- W2884203481 hasConceptScore W2884203481C111113717 @default.
- W2884203481 hasConceptScore W2884203481C112705442 @default.
- W2884203481 hasConceptScore W2884203481C116569031 @default.
- W2884203481 hasConceptScore W2884203481C151730666 @default.
- W2884203481 hasConceptScore W2884203481C170493617 @default.
- W2884203481 hasConceptScore W2884203481C185592680 @default.
- W2884203481 hasConceptScore W2884203481C202751555 @default.
- W2884203481 hasConceptScore W2884203481C207001950 @default.
- W2884203481 hasConceptScore W2884203481C2779343474 @default.
- W2884203481 hasConceptScore W2884203481C2780035454 @default.
- W2884203481 hasConceptScore W2884203481C54355233 @default.
- W2884203481 hasConceptScore W2884203481C55493867 @default.
- W2884203481 hasConceptScore W2884203481C57992300 @default.
- W2884203481 hasConceptScore W2884203481C64903051 @default.
- W2884203481 hasConceptScore W2884203481C70721500 @default.
- W2884203481 hasConceptScore W2884203481C74187038 @default.
- W2884203481 hasConceptScore W2884203481C86803240 @default.
- W2884203481 hasConceptScore W2884203481C98274493 @default.
- W2884203481 hasLocation W28842034811 @default.
- W2884203481 hasLocation W28842034812 @default.
- W2884203481 hasOpenAccess W2884203481 @default.
- W2884203481 hasPrimaryLocation W28842034811 @default.
- W2884203481 hasRelatedWork W1978032370 @default.
- W2884203481 hasRelatedWork W1979757582 @default.
- W2884203481 hasRelatedWork W1998587742 @default.
- W2884203481 hasRelatedWork W2010793381 @default.
- W2884203481 hasRelatedWork W2067960249 @default.
- W2884203481 hasRelatedWork W2329258414 @default.
- W2884203481 hasRelatedWork W2332367370 @default.
- W2884203481 hasRelatedWork W2400461952 @default.
- W2884203481 hasRelatedWork W2953758866 @default.
- W2884203481 hasRelatedWork W79555446 @default.
- W2884203481 hasVolume "835" @default.
- W2884203481 isParatext "false" @default.
- W2884203481 isRetracted "false" @default.
- W2884203481 magId "2884203481" @default.
- W2884203481 workType "article" @default.