Absolute bioavailability and stereoselective pharmacokinetics of doxepin
Bibliographic record
Abstract
1. Commercial doxepin contains geometric isomers in the proportions Z:E = 15:85. Z-doxepin and its metabolite Z-N-desmethyldoxepin are both active antidepressants, whereas the corresponding E-isomers are less active therapeutically. 2. The present pharmacokinetic study was a balanced, randomized, two-treatment, two-period, two-sequence crossover design in which 12 healthy male volunteers were given single doses of commercial doxepin intravenously and orally on two occasions separated by a washout period. 3. A two-compartment model with no lag time and first-order elimination fitted the plasma concentration-time curves after intravenous dosing. Pharmacokinetic parameters estimated from the model were comparable with those estimated by non-compartmental methods. 4. All pharmacokinetic parameters displayed a wide between-subject variability. Both isomers of doxepin showed large volumes of distribution and relatively short half-lives in plasma, suggestive of extensive distribution and/or tissue binding. The mean fraction absorbed after oral administration was 0.29 for each isomer. Renal clearances of each isomer were very low after either oral or intravenous dosing, although all four analytes were quantifiable in the urine for prolonged periods. 5. After oral dosing, plasma concentrations of the doxepin isomers remained roughly in the ratio Z:E = 15:85, whereas those of N-desmethyldoxepin were closer to 1:1 in all but two outliers, who had high levels E-N-desmethyldoxepin.
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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 | 0.000 | 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 | 0.000 |
| 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 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".