A convenient five‐drug cocktail for the assessment of major drug metabolizing enzymes: a pilot study
Bibliographic record
Abstract
AIMS: To assess the feasibility of administering at the same time low doses of five probe drugs, metoprolol (25 mg), chlorzoxazone (250 mg), tolbutamide (250 mg), dapsone (100 mg) and caffeine (100 mg) to determine simultaneously the activities of CYP2D6, CYP2E1, CYP2C9, CYP3A4, CYP1A2, N-acetyltransferase-2 and xanthine oxidase. METHODS: Ten healthy young non-smoking males received the following drugs or combinations of drugs over a 5-week period: week 1) metoprolol; 2) tolbutamide; 3) caffeine, chlorzoxazone and dapsone; 4) caffeine, chlorzoxazone, dapsone and metoprolol; 5) caffeine, chlorzoxazone, dapsone, metoprolol and tolbutamide. The drugs were self-administered at bedtime and urine was collected for the following 8 h. RESULTS: Mean molar phenotypic ratios obtained after administering metoprolol (mean change of -11%) or tolbutamide (mean change of -0.3%) alone, were not significantly different from those obtained when other drugs were co-administered (P > 0.05). The mean within-subject coefficients of variation were 33%, 18%, 22%, 13%, 16%, 13% and 5% for CYP3A4, CYP2D6, CYP2C9, CYP2E1, CYP1A2, N-acetyltransferase 2 and xanthine oxidase metabolic ratios, respectively. No significant interactions (P > 0.5) were observed during the simultaneous administration of various combinations of the five probe drugs. CONCLUSIONS: We propose that this cocktail, composed of five widely available drugs, constitutes a promising means of simultaneously determining the activities of the major CYP enzymes in large populations.
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How this classification was reachedexpand
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 | 0.012 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.003 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".