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Record W4390034467 · doi:10.21203/rs.3.rs-3632769/v1

Mechanism of the first and second peaks in epinephrine pharmacokinetics over time

2023· preprint· en· W4390034467 on OpenAlexaff
Richard F. Lockey, Anne K. Ellis, Richard Lowenthal, Sarina Tanimoto

Bibliographic record

VenueResearch Square · 2023
Typepreprint
Languageen
FieldMedicine
TopicDrug-Induced Adverse Reactions
Canadian institutionsQueen's University
Fundersnot available
KeywordsEpinephrinePharmacokineticsMedicineAnesthesiaChemistryInternal medicine

Abstract

fetched live from OpenAlex

Abstract Background : There is a documented double peak phenomenon following the intramuscular injection of epinephrine, however these peaks are typically representative of mean epinephrine concentrations and not individual subjects. Objective : An examination of epinephrine pharmacokinetics was conducted to explore the nature of the double peak phenomenon and to determine if the double peaks observed in mean concentration profiles were also observed in individual subjects. Methods : A GCP compliant study was conducted in 36 adult volunteers with a history of type I allergies. Blood samples were collected before and at multiple timepoints after subjects self- administered two FDA-approved epinephrine auto-injectors (EpiPen 0.3 mg and Symjepi 0.3 mg). Pharmacokinetic parameters (C max and t max ) and concentration-time curves were determined based on individual subjects. Subjects were categorized by their t max (≤4 min, >4 min - ≤10 min, >10 min - ≤20 min, >20 min - ≤30 min, >30 min - ≤45 min, and >45 min, presented as ≤4 min, ≤10 min, ≤20 min, ≤30 min, ≤45 min, and >45 min, respectively). Results : The majority of individual subjects did not have double peaks. Double peaks in mean concentration-time profiles were observed when t max was ≤4 min following EpiPen and Symjepi, t max ≤30 min following EpiPen, and t max ≤45 min following EpiPen. The individual epinephrine concentration curves for subjects with a t max ≤4 min following EpiPen and Symjepi and t max ≤45 min following EpiPen demonstrate that the majority of individual subjects do not have double peaks. Conclusion : These data suggest that the double peaks observed in mean epinephrine concentrations are likely driven by subsets of subjects with either early or late t max values and may not necessarily be a pharmacokinetic characteristic of epinephrine.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.691
Threshold uncertainty score0.998

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.002
Research integrity0.0000.002
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.075
GPT teacher head0.402
Teacher spread0.326 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2023
Admission routes1
Has abstractyes

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