CYP2B6 and Bupropion’s Smoking-Cessation Pharmacology: The Role of Hydroxybupropion
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
Bupropion is indicated to promote smoking cessation. Animal studies suggest that the pharmacologic activity of bupropion can be mediated by its major metabolite, hydroxybupropion. We measured plasma bupropion and its metabolite levels in a double-blind, placebo controlled, randomized smoking-cessation trial. Among the treatment-adherent individuals, higher hydroxybupropion concentrations (per μg/ml) resulted in better smoking-cessation outcomes (week 3, 7, and 26 odds ratio (OR) = 2.82, 2.96, and 2.37, respectively, P = 0.005-0.040); this was not observed with bupropion levels (OR = 1.00-1.03, P = 0.59-0.90). Genetic variation in CYP2B6, the enzyme that metabolizes bupropion to hydroxybupropion, was identified as a significant source of variability in hydroxybupropion formation. Our data indicate that hydroxybupropion contributes to the pharmacologic effects of bupropion for smoking cessation, and that variability in response to bupropion treatment is related to variability in CYP2B6-mediated hydroxybupropion formation. These findings suggest that dosing of bupropion to achieve a hydroxybupropion level of 0.7 μg/ml or increasing bupropion dose for CYP2B6 slow metabolizers could improve bupropion's cessation outcomes.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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