Metabolism of Atypical Antipsychotics: Involvement of Cytochrome P450 Enzymes and Relevance for Drug-Drug Interactions
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Full frame distilled prediction
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.
- Candidate categories
- Meta-epidemiology (narrow)
- Consensus categories
- Meta-epidemiology (narrow)
- Domain
- Candidate signal: noneConsensus signal: none
- Study design
- Candidate signal: Not applicableConsensus signal: none
- Genre
- Candidate signal: ReviewConsensus signal: Review
- Teacher disagreement score
- 0.947
- Threshold uncertainty score
- 1.000
- Validation status
machine_predicted_unvalidated·codex-gemma-dda1882f352a
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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.
- Teacher spread
- 0.292 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
The involvement of cytochrome P450 (CYP) enzymes in the metabolism of the atypical (second-generation) antipsychotics clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone and amisulpride is reviewed, and the possible relevance of this metabolism to drug-drug interactions is discussed. Clozapine is metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4. Risperidone is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4; the 9-hydroxy metabolite of risperidone (paliperidone) is now marketed as an antipsychotic in its own right. Olanzapine is metabolized primarily by direct glucuronidation and CYP1A2 and to a lesser extent by CYP2D6 and CYP3A4. Quetiapine is metabolized by CYP3A4, as is ziprasidone, although in the latter case aldehyde oxidase is the enzyme responsible for most of the metabolism. CYP2D6 and CYP3A4 are important in the metabolism of aripiprazole, and CYP-catalyzed metabolism of paliperidone and amisulpride appears to be minor. At the usual clinical doses, these drugs appear to not generally affect markedly the metabolism of other coadministered medications. However, as indicated above, several of atypical antipsychotics are metabolized by CYP enzymes, and physicians should be aware of coadministered drugs that may inhibit or induce these CYP enzymes; examples of such possible interactions are presented in this review.
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.
The record
- Venue
- Current Drug Metabolism
- Topic
- Pharmacogenetics and Drug Metabolism
- Field
- Pharmacology, Toxicology and Pharmaceutics
- Canadian institutions
- University of Alberta
- Funders
- Canadian Institutes of Health Research
- Keywords
- ZiprasidoneQuetiapineAripiprazoleAmisulpridePharmacologyOlanzapineClozapineAtypical antipsychoticRisperidoneAsenapinePaliperidoneSertindoleCYP3A4ChemistryCYP2D6Drug metabolismAntipsychoticCytochrome P450MedicineDrugMetabolismBiochemistryPsychiatrySchizophrenia (object-oriented programming)
- Has abstract in OpenAlex
- yes