Variability of the In Vivo Metabolism of Clozapine
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
OBJECTIVES: Clozapine, the gold standard of antipsychotic treatment in treatment-refractory patients with schizophrenia, is metabolized in vivo to clozapine-N-oxide and N-desmethylclozapine (NDMC = norclozapine). N-desmethylclozapine is an active metabolite of clozapine and combines unique pharmacological properties. Because little is known about the rate of metabolic conversion of clozapine in vivo, we assessed the association between clozapine dose and plasma levels for clozapine and NDMC. METHODS: Plasma levels of clozapine and NDMC were measured in 485 blood samples from 108 patients with schizophrenia treated with clozapine. %NDMC, the ratio of NDMC to total clozapine (NDMC + clozapine), was used as a measure of the in vivo metabolism of clozapine. RESULTS: Daily clozapine doses correlated significantly with clozapine levels and NDMC levels, whereas %NDMC showed a weaker negative correlation with clozapine dose. The mean %NDMC value was 37.0% +/- 16.8%, with high variability between subjects. Repeated measurements in subjects treated with the same dose of clozapine showed a high within-subject variability of %NDMC. CONCLUSIONS: Our results suggest a high degree of between-subject and within-subject variability in the metabolism of clozapine in vivo. Direct administration of NDMC may be preferable to reliably achieve sufficient plasma levels of this compound.
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Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
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