FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2765855720> ?p ?o ?g. }

• W2765855720 abstract "To develop a population pharmacokinetic/pharmacodynamic (PPK/PD) model for E2027, a selective PDE9 inhibitor, following single ascending oral doses in healthy volunteers (HV), which will be used to drive dose selection in subsequent studies. Plasma concentration-time data of E2027, from a 4-part randomized, double blind, placebo-controlled, single ascending dose, Phase 1 study in HV, were subjected to population PK analysis by nonlinear mixed effect modeling. The effects of various baseline, demographic characteristics and dose on PK were evaluated. Post-hoc estimates of final PPK parameters were used in subsequent development of a population PK/PD (PPK/PD) model to describe the changes in cerebrospinal fluid (CSF) cGMP concentrations over time. The final PK and PPK/PD models were used to predict E2027 steady-state exposures and percent increase in CSF cGMP from baseline following multiple oral doses. The PK of E2027 was best described by a 2 compartment model with two input functions with five transit compartments, and first-order elimination. All parameters were estimated with good precision (CV% <10%). Weight, gender, and dose (>200 mg) significantly affected the PK of E2027. Percent CSF cGMP changes from baseline were best described by a sigmoidal inhibitory Emax model on kout, with IC50 of 118 ng/mL, and Imax of 0.813. Although, the PPK and PPK/PD models are being updated with PK and PD data from multiple ascending dose studies, simulations using the currently developed PPK/PD model suggest that once-daily E2027 dosed at, or above 100 mg should maintain cGMP at a 3-fold increase from baseline. A PPK/PD model for E2027 was successfully developed. This model supports selection of once daily doses for proof of concept studies, demonstrating target engagement that provides adequate CSF cGMP level elevations." @default.
• W2765855720 created "2017-11-10" @default.
• W2765855720 creator A5001447538 @default.
• W2765855720 creator A5010189987 @default.
• W2765855720 creator A5022334220 @default.
• W2765855720 creator A5028315849 @default.
• W2765855720 creator A5037889416 @default.
• W2765855720 creator A5038677280 @default.
• W2765855720 creator A5045365891 @default.
• W2765855720 creator A5072708912 @default.
• W2765855720 creator A5085639542 @default.
• W2765855720 date "2017-07-01" @default.
• W2765855720 modified "2023-09-28" @default.
• W2765855720 title "[P1-056]: POPULATION PHARMACOKINETIC-PHARMACODYNAMIC (PK/PD) MODELING OF E2027, A SELECTIVE PHOSPHODIESTERASE-9 (PDE9) INHIBITOR, FOLLOWING SINGLE ASCENDING ORAL DOSES IN HEALTHY VOLUNTEERS" @default.
• W2765855720 doi "https://doi.org/10.1016/j.jalz.2017.06.123" @default.
• W2765855720 hasPublicationYear "2017" @default.
• W2765855720 type Work @default.
• W2765855720 sameAs 2765855720 @default.
• W2765855720 citedByCount "1" @default.
• W2765855720 countsByYear W27658557202023 @default.
• W2765855720 crossrefType "journal-article" @default.
• W2765855720 hasAuthorship W2765855720A5001447538 @default.
• W2765855720 hasAuthorship W2765855720A5010189987 @default.
• W2765855720 hasAuthorship W2765855720A5022334220 @default.
• W2765855720 hasAuthorship W2765855720A5028315849 @default.
• W2765855720 hasAuthorship W2765855720A5037889416 @default.
• W2765855720 hasAuthorship W2765855720A5038677280 @default.
• W2765855720 hasAuthorship W2765855720A5045365891 @default.
• W2765855720 hasAuthorship W2765855720A5072708912 @default.
• W2765855720 hasAuthorship W2765855720A5085639542 @default.
• W2765855720 hasBestOaLocation W27658557201 @default.
• W2765855720 hasConcept C111113717 @default.
• W2765855720 hasConcept C112705442 @default.
• W2765855720 hasConcept C142724271 @default.
• W2765855720 hasConcept C204787440 @default.
• W2765855720 hasConcept C27081682 @default.
• W2765855720 hasConcept C2908647359 @default.
• W2765855720 hasConcept C71924100 @default.
• W2765855720 hasConcept C76318530 @default.
• W2765855720 hasConcept C98274493 @default.
• W2765855720 hasConcept C99454951 @default.
• W2765855720 hasConceptScore W2765855720C111113717 @default.
• W2765855720 hasConceptScore W2765855720C112705442 @default.
• W2765855720 hasConceptScore W2765855720C142724271 @default.
• W2765855720 hasConceptScore W2765855720C204787440 @default.
• W2765855720 hasConceptScore W2765855720C27081682 @default.
• W2765855720 hasConceptScore W2765855720C2908647359 @default.
• W2765855720 hasConceptScore W2765855720C71924100 @default.
• W2765855720 hasConceptScore W2765855720C76318530 @default.
• W2765855720 hasConceptScore W2765855720C98274493 @default.
• W2765855720 hasConceptScore W2765855720C99454951 @default.
• W2765855720 hasIssue "7S_Part_5" @default.
• W2765855720 hasLocation W27658557201 @default.
• W2765855720 hasOpenAccess W2765855720 @default.
• W2765855720 hasPrimaryLocation W27658557201 @default.
• W2765855720 hasRelatedWork W1758514097 @default.
• W2765855720 hasRelatedWork W1997101420 @default.
• W2765855720 hasRelatedWork W2002058825 @default.
• W2765855720 hasRelatedWork W2010116591 @default.
• W2765855720 hasRelatedWork W2066320494 @default.
• W2765855720 hasRelatedWork W2142080078 @default.
• W2765855720 hasRelatedWork W2227061539 @default.
• W2765855720 hasRelatedWork W2594910449 @default.
• W2765855720 hasRelatedWork W2992709639 @default.
• W2765855720 hasRelatedWork W4285393230 @default.
• W2765855720 hasVolume "13" @default.
• W2765855720 isParatext "false" @default.
• W2765855720 isRetracted "false" @default.
• W2765855720 magId "2765855720" @default.
• W2765855720 workType "article" @default.