Matches in SemOpenAlex for { <https://semopenalex.org/work/W2038349110> ?p ?o ?g. }
- W2038349110 endingPage "17" @default.
- W2038349110 startingPage "1" @default.
- W2038349110 abstract "Active efflux transport processes at the blood–brain barrier (BBB), such as P-glycoprotein (P-gp)-mediated efflux, can limit brain uptake of therapeutics. Accurate determination of the consequent impact on brain uptake is assumed to require sampling post-attainment of brain-to-blood distribution equilibrium. Because this approach is not always feasible, understanding the relationship between apparent degree of efflux (e.g., calculated BBB P-gp effect) and the fraction of time remaining until distribution equilibrium is achieved (FTDE) would be advantageous. This study employed simulation strategies to explore this relationship in the simplest relevant system (absence of protein binding, saturable uptake, or metabolism at the BBB). Concentration-time profiles were simulated with a 4-compartment system (blood, peripheral tissues, BBB endothelium and brain parenchyma). A unidirectional endothelium-to-blood rate constant, PSe, represented P-gp-mediated efflux. A parameter space was selected to simulate an 18-fold P-gp effect, (Kp,brain at distribution equilibrium in the absence [Kp,brain = 82] vs. presence [Kp,brain = 4.5] of P-gp-mediated flux), as observed for paclitaxel in P-gp-deficient vs. P-gp-competent mice. Hypothetical compounds with different P-gp effects, peripheral compartment distribution kinetics, or times to achieve distribution equilibrium were simulated by perturbing the values of relevant model parameters. P-gp effects calculated prior to attainment of distribution equilibrium may be substantially erroneous. However, reasonably accurate estimates can be obtained relatively early in the net distributional phase (under 20% error at FTDE > 0.36 or 0.11 for bolus or infusion administration, respectively). Potential errors associated with non-equilibrium calculations are dependent on both P-gp-mediated and P-gp-independent components of flux across the BBB." @default.
- W2038349110 created "2016-06-24" @default.
- W2038349110 creator A5038446642 @default.
- W2038349110 creator A5049414071 @default.
- W2038349110 date "2011-12-01" @default.
- W2038349110 modified "2023-09-26" @default.
- W2038349110 title "Influence of time to achieve substrate distribution equilibrium between brain tissue and blood on quantitation of the blood–brain barrier P-glycoprotein effect" @default.
- W2038349110 cites W113678817 @default.
- W2038349110 cites W1486779292 @default.
- W2038349110 cites W1580448123 @default.
- W2038349110 cites W171460375 @default.
- W2038349110 cites W176733150 @default.
- W2038349110 cites W1967839568 @default.
- W2038349110 cites W1972574941 @default.
- W2038349110 cites W1977073394 @default.
- W2038349110 cites W1981471107 @default.
- W2038349110 cites W1991064261 @default.
- W2038349110 cites W2005176690 @default.
- W2038349110 cites W2015574368 @default.
- W2038349110 cites W2016812290 @default.
- W2038349110 cites W2019695588 @default.
- W2038349110 cites W2022314390 @default.
- W2038349110 cites W2030028063 @default.
- W2038349110 cites W2034767995 @default.
- W2038349110 cites W2036128821 @default.
- W2038349110 cites W2036678718 @default.
- W2038349110 cites W2051651821 @default.
- W2038349110 cites W2054992843 @default.
- W2038349110 cites W2062195390 @default.
- W2038349110 cites W2065602348 @default.
- W2038349110 cites W2081577644 @default.
- W2038349110 cites W2082810911 @default.
- W2038349110 cites W2098023573 @default.
- W2038349110 cites W2101193630 @default.
- W2038349110 cites W2102790064 @default.
- W2038349110 cites W2103467580 @default.
- W2038349110 cites W2108141803 @default.
- W2038349110 cites W2108486409 @default.
- W2038349110 cites W2109134169 @default.
- W2038349110 cites W2112001901 @default.
- W2038349110 cites W2112820588 @default.
- W2038349110 cites W2117024164 @default.
- W2038349110 cites W2128540492 @default.
- W2038349110 cites W2134344823 @default.
- W2038349110 cites W2134756034 @default.
- W2038349110 cites W2135063623 @default.
- W2038349110 cites W2144391411 @default.
- W2038349110 cites W2157635452 @default.
- W2038349110 cites W2163636362 @default.
- W2038349110 cites W2166153381 @default.
- W2038349110 cites W2416586998 @default.
- W2038349110 doi "https://doi.org/10.1016/j.brainres.2011.10.009" @default.
- W2038349110 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22036081" @default.
- W2038349110 hasPublicationYear "2011" @default.
- W2038349110 type Work @default.
- W2038349110 sameAs 2038349110 @default.
- W2038349110 citedByCount "10" @default.
- W2038349110 countsByYear W20383491102012 @default.
- W2038349110 countsByYear W20383491102013 @default.
- W2038349110 countsByYear W20383491102015 @default.
- W2038349110 countsByYear W20383491102018 @default.
- W2038349110 countsByYear W20383491102022 @default.
- W2038349110 countsByYear W20383491102023 @default.
- W2038349110 crossrefType "journal-article" @default.
- W2038349110 hasAuthorship W2038349110A5038446642 @default.
- W2038349110 hasAuthorship W2038349110A5049414071 @default.
- W2038349110 hasConcept C110121322 @default.
- W2038349110 hasConcept C12554922 @default.
- W2038349110 hasConcept C126322002 @default.
- W2038349110 hasConcept C133936738 @default.
- W2038349110 hasConcept C134018914 @default.
- W2038349110 hasConcept C134306372 @default.
- W2038349110 hasConcept C185592680 @default.
- W2038349110 hasConcept C200082930 @default.
- W2038349110 hasConcept C2778402981 @default.
- W2038349110 hasConcept C2778707650 @default.
- W2038349110 hasConcept C33923547 @default.
- W2038349110 hasConcept C43376680 @default.
- W2038349110 hasConcept C501593827 @default.
- W2038349110 hasConcept C529278444 @default.
- W2038349110 hasConcept C55493867 @default.
- W2038349110 hasConcept C71924100 @default.
- W2038349110 hasConcept C86803240 @default.
- W2038349110 hasConceptScore W2038349110C110121322 @default.
- W2038349110 hasConceptScore W2038349110C12554922 @default.
- W2038349110 hasConceptScore W2038349110C126322002 @default.
- W2038349110 hasConceptScore W2038349110C133936738 @default.
- W2038349110 hasConceptScore W2038349110C134018914 @default.
- W2038349110 hasConceptScore W2038349110C134306372 @default.
- W2038349110 hasConceptScore W2038349110C185592680 @default.
- W2038349110 hasConceptScore W2038349110C200082930 @default.
- W2038349110 hasConceptScore W2038349110C2778402981 @default.
- W2038349110 hasConceptScore W2038349110C2778707650 @default.
- W2038349110 hasConceptScore W2038349110C33923547 @default.
- W2038349110 hasConceptScore W2038349110C43376680 @default.
- W2038349110 hasConceptScore W2038349110C501593827 @default.
- W2038349110 hasConceptScore W2038349110C529278444 @default.
- W2038349110 hasConceptScore W2038349110C55493867 @default.