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An investigation of morphine‐to‐codeine metabolic ratios in postmortem blood, drug interactions, and cytochrome P450 2D6 (CYP2D6) genotype

2013· article· en· W3172196938 on OpenAlexaffabout
Jessica Lam, Karen L. Woodall, Patricia Solbeck, Colin J.D. Ross, Bruce Carleton, Michael R. Hayden, Gideon Koren, Parvaz Madadi

Bibliographic record

VenueThe FASEB Journal · 2013
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacogenetics and Drug Metabolism
Canadian institutionsChild and Family Research InstituteChildren's & Women's Health Centre of British ColumbiaUniversity of British ColumbiaAdvantage Forensics (Canada)Hospital for Sick Children
Fundersnot available
KeywordsCodeineMorphineCYP2D6MedicineForensic toxicologyGenotypePharmacologyOpioidDrugHeroinAnesthesiaInternal medicineBiologyCytochrome P450GeneChemistryGenetics

Abstract

fetched live from OpenAlex

The objective of this study was to investigate the correlation between CYP2D6 genotype, drug interactions, and morphine‐to‐codeine metabolic ratio (MR) in codeine‐related deaths (CRD). The records of the Office of the Chief Coroner of Ontario were examined to identify all CRD from 2006–2008. Deaths in which codeine and its metabolite, morphine, were quantified on the toxicological screen were included. From these, cases in which the manner of death was undetermined, heroin use was suspected, and/or morphine use was suspected were excluded. A total of 59 CRD were included. Postmortem blood samples were analyzed for 17 polymorphisms in CYP2D6 as well as gene duplication. The frequencies of CYP2D6 ultrarapid, extensive, intermediate, and poor metabolizer (PM) was not different in CRDs and a previously published healthy cohort taking opioids. Alcohol use prior to death was significantly associated with CRD that were deemed to be accidental by the coroner (p=0.05). The presence of a selective‐serotonin reuptake inhibitor was significantly associated with suicides (p=0.014). PM was associated with low MR. These findings suggest that CYP2D6 genotype and drug interactions should considered as part of the postmortem toxicological interpretation for CRD, especially in cases with low or high MR.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.023

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
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 science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.053
GPT teacher head0.374
Teacher spread0.321 · 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 source (direct Gemma or distilled Codex), 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
Published2013
Admission routes2
Has abstractyes

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