Matches in SemOpenAlex for { <https://semopenalex.org/work/W3045588410> ?p ?o ?g. }
Showing items 1 to 100 of
100
with 100 items per page.
- W3045588410 endingPage "2" @default.
- W3045588410 startingPage "1" @default.
- W3045588410 abstract "OBJECTIVES/GOALS: Allopregnanolone (ALLO), a modulator of GABA A receptors, may be useful as a treatment for human and canine benzodiazepine-refractory status epilepticus (SE). Our objective was to develop a phamacokinetic-pharmacodynamic (PKPD) model relating ALLO plasma concentrations to electroencephalographic (EEG) effects in dogs. METHODS/STUDY POPULATION: Four healthy dogs and one dog with epilepsy that had implanted intracranial electrodes were utilized. ALLO doses ranging from 1-6 mg/kg were administered IV over 5 min. EEG data were collected during four IM doses (1-2 mg/kg). Blood samples were collected up to 6 hr following dosing. ALLO concentrations were measured using HPLC-MS/MS. Power density was determined in EEG bands using a custom algorithm. A two-compartment link PKPD model was developed to describe the relation between ALLO plasma concentration and change in EEG power in the alpha, beta, delta and theta bands. RESULTS/ANTICIPATED RESULTS: ALLO caused a rapid increase in absolute power density in all EEG bands measured (1-4, >4 – 8, >8 – 12, >12 – 25, and >25 – 100 Hz). The onset of effect was rapid (1-3 min) and demonstrated by frequency band and dose analysis. Concentration-EEG data were best fit by a two-compartment PK model and sigmoidal Emax PD indirect link model. The beta frequency band was most sensitive, showing increases in power at the lowest ALLO concentrations. The EC50 concentration for the beta frequency was ~270 ng/mL. The EC50 values for effects on the other frequency bands were ~500-700 ng /mL. In conclusion, IV ALLO causes a rapid effect on EEG that can be used to determine minimal plasma concentrations associated with target engagement. DISCUSSION/SIGNIFICANCE OF IMPACT: Dose selection for future clinical trials will use the effective concentrations determined here in conjunction with studies in animal status epilepticus models. Studies are planned in client owned dogs with epilepsy to evaluate clinical efficacy in dogs and as nonclinical proof-of-concept evidence supporting translational studies in people. CONFLICT OF INTEREST DESCRIPTION: Michael Rogawski and Dorota Zolkowska are named as inventors on patent applications claiming use of neuroactive steroids including allopregnanolone and ganaxolone in the treatment of status epilepticus." @default.
- W3045588410 created "2020-08-03" @default.
- W3045588410 creator A5008904502 @default.
- W3045588410 creator A5022508298 @default.
- W3045588410 creator A5023390509 @default.
- W3045588410 creator A5032842851 @default.
- W3045588410 creator A5044523433 @default.
- W3045588410 creator A5056015753 @default.
- W3045588410 creator A5058266378 @default.
- W3045588410 creator A5087490307 @default.
- W3045588410 date "2020-06-01" @default.
- W3045588410 modified "2023-09-22" @default.
- W3045588410 title "4512 Allopregnanolone Dose Finding for Status Epilepticus Treatment by Pharmacokinetic-Pharmacodynamic Modeling using Quantitative EEG in Dogs" @default.
- W3045588410 doi "https://doi.org/10.1017/cts.2020.51" @default.
- W3045588410 hasPublicationYear "2020" @default.
- W3045588410 type Work @default.
- W3045588410 sameAs 3045588410 @default.
- W3045588410 citedByCount "0" @default.
- W3045588410 crossrefType "journal-article" @default.
- W3045588410 hasAuthorship W3045588410A5008904502 @default.
- W3045588410 hasAuthorship W3045588410A5022508298 @default.
- W3045588410 hasAuthorship W3045588410A5023390509 @default.
- W3045588410 hasAuthorship W3045588410A5032842851 @default.
- W3045588410 hasAuthorship W3045588410A5044523433 @default.
- W3045588410 hasAuthorship W3045588410A5056015753 @default.
- W3045588410 hasAuthorship W3045588410A5058266378 @default.
- W3045588410 hasAuthorship W3045588410A5087490307 @default.
- W3045588410 hasBestOaLocation W30455884101 @default.
- W3045588410 hasConcept C111113717 @default.
- W3045588410 hasConcept C112705442 @default.
- W3045588410 hasConcept C118552586 @default.
- W3045588410 hasConcept C126322002 @default.
- W3045588410 hasConcept C141071460 @default.
- W3045588410 hasConcept C168258287 @default.
- W3045588410 hasConcept C170493617 @default.
- W3045588410 hasConcept C185592680 @default.
- W3045588410 hasConcept C199360897 @default.
- W3045588410 hasConcept C2775944032 @default.
- W3045588410 hasConcept C2776174256 @default.
- W3045588410 hasConcept C2777288759 @default.
- W3045588410 hasConcept C2777341932 @default.
- W3045588410 hasConcept C2778186239 @default.
- W3045588410 hasConcept C2778338918 @default.
- W3045588410 hasConcept C2908647359 @default.
- W3045588410 hasConcept C41008148 @default.
- W3045588410 hasConcept C42219234 @default.
- W3045588410 hasConcept C44796713 @default.
- W3045588410 hasConcept C49453240 @default.
- W3045588410 hasConcept C522805319 @default.
- W3045588410 hasConcept C64943373 @default.
- W3045588410 hasConcept C71924100 @default.
- W3045588410 hasConcept C98274493 @default.
- W3045588410 hasConcept C99454951 @default.
- W3045588410 hasConceptScore W3045588410C111113717 @default.
- W3045588410 hasConceptScore W3045588410C112705442 @default.
- W3045588410 hasConceptScore W3045588410C118552586 @default.
- W3045588410 hasConceptScore W3045588410C126322002 @default.
- W3045588410 hasConceptScore W3045588410C141071460 @default.
- W3045588410 hasConceptScore W3045588410C168258287 @default.
- W3045588410 hasConceptScore W3045588410C170493617 @default.
- W3045588410 hasConceptScore W3045588410C185592680 @default.
- W3045588410 hasConceptScore W3045588410C199360897 @default.
- W3045588410 hasConceptScore W3045588410C2775944032 @default.
- W3045588410 hasConceptScore W3045588410C2776174256 @default.
- W3045588410 hasConceptScore W3045588410C2777288759 @default.
- W3045588410 hasConceptScore W3045588410C2777341932 @default.
- W3045588410 hasConceptScore W3045588410C2778186239 @default.
- W3045588410 hasConceptScore W3045588410C2778338918 @default.
- W3045588410 hasConceptScore W3045588410C2908647359 @default.
- W3045588410 hasConceptScore W3045588410C41008148 @default.
- W3045588410 hasConceptScore W3045588410C42219234 @default.
- W3045588410 hasConceptScore W3045588410C44796713 @default.
- W3045588410 hasConceptScore W3045588410C49453240 @default.
- W3045588410 hasConceptScore W3045588410C522805319 @default.
- W3045588410 hasConceptScore W3045588410C64943373 @default.
- W3045588410 hasConceptScore W3045588410C71924100 @default.
- W3045588410 hasConceptScore W3045588410C98274493 @default.
- W3045588410 hasConceptScore W3045588410C99454951 @default.
- W3045588410 hasIssue "s1" @default.
- W3045588410 hasLocation W30455884101 @default.
- W3045588410 hasLocation W30455884102 @default.
- W3045588410 hasOpenAccess W3045588410 @default.
- W3045588410 hasPrimaryLocation W30455884101 @default.
- W3045588410 hasRelatedWork W1988935887 @default.
- W3045588410 hasRelatedWork W1990079369 @default.
- W3045588410 hasRelatedWork W2021831895 @default.
- W3045588410 hasRelatedWork W2096040265 @default.
- W3045588410 hasRelatedWork W2152560731 @default.
- W3045588410 hasRelatedWork W2207503964 @default.
- W3045588410 hasRelatedWork W2899072855 @default.
- W3045588410 hasRelatedWork W2922882148 @default.
- W3045588410 hasRelatedWork W2997938974 @default.
- W3045588410 hasRelatedWork W2108030623 @default.
- W3045588410 hasVolume "4" @default.
- W3045588410 isParatext "false" @default.
- W3045588410 isRetracted "false" @default.
- W3045588410 magId "3045588410" @default.
- W3045588410 workType "article" @default.