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Record W2131567043 · doi:10.1080/03602530600959615

Evaluation of Which Reactive Metabolite, If Any, Is Responsible for a Specific Idiosyncratic Reaction

2006· review· en· W2131567043 on OpenAlexaff
Jack Uetrecht

Bibliographic record

VenueDrug Metabolism Reviews · 2006
Typereview
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacogenetics and Drug Metabolism
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsMetaboliteReactive intermediateCircumstantial evidenceDrug reactionMechanism (biology)ChemistryDrugPharmacologyBiochemistryBiologyEpistemology

Abstract

fetched live from OpenAlex

Reactive metabolites are believed to be responsible for most idiosyncratic drug reactions. It is often assumed that if a reactive metabolite is found, it must be responsible for the idiosyncratic reactions associated with that drug. However, the evidence linking reactive metabolites and idiosyncratic reactions is circumstantial at best, and in many cases we have virtually no evidence. Furthermore, it is common for a drug to form several reactive metabolites, so it can be difficult to determine which, if any, is responsible for a given idiosyncratic reaction. Although the reactive metabolite hypothesis is logical, it has important implications for drug development, and we need to develop ways to test the hypothesis for specific drugs rigorously. Valid animal models are a powerful tool for testing whether a specific reactive metabolite is responsible for a specific adverse reaction and for studying further the mechanism by which it may induce such reactions; however, such models are rare.

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)0.030
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Meta-epidemiology (narrow), Research integrity
Consensus categoriesMeta-epidemiology (narrow)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.948
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0300.002
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0080.003
Bibliometrics0.0010.003
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.002
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 head0.333
GPT teacher head0.518
Teacher spread0.185 · 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; both teacher heads agree on what is shown here.

Study designNot applicable
Domainnot available
GenreReview

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

Citations51
Published2006
Admission routes1
Has abstractyes

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