Pharmacokinetics and Metabolism of Zopiclone
Bibliographic record
Abstract
Pharmacokinetics and metabolism of a new hypnotic, zopiclone (ZD), were studied under the following conditions: (1) rats and dogs were given oral doses of the molecule, 14C-labeled either on the side chain or on the pyrrolopyrazine nucleus; (2) rats, rabbits and dogs were given increasing oral doses of the cold compound; (3) human subjects in various physiopathological situations--young and elderly healthy volunteers, patients with liver or renal impairments, nursing mothers--were given single or repeated doses, p.o. or i.v. (range 3.5-15 mg). ZD is rapidly and efficiently absorbed: its oral bioavailability was greater than 75% in all species except rats, where a first-pass effect of about 65% was recorded. Plasma protein binding is about 45%. The radioactive material rapidly diffuses from the vascular compartment, with a marked affinity for the brain. Plasma kinetics of ZD are generally well described by a two-compartment open model; in man, terminal half-life is 4-5 h; total body clearance is large (300 ml/mn), renal clearance very low (10 ml/min). The relationship between doses and concentrations, doses and urinary excretion of unchanged compound and major metabolites was linear in all species, except rabbits. The major metabolic routes involve decarboxylation affecting more than 50% of dose (rats and dogs), N-demethylation and N-oxidation--more than 30% as N-desmethyl and N-oxide derivatives in urine (humans). Due to intensive metabolism, only 7-10% of the dose is recovered in urine and feces as unchanged compounds (all species). In nursing mothers, milk and plasma kinetics of ZD are similar with a milk/plasma ratio around 0.80. In human volunteers, plasma half-life of ZD increases with age, while patients with liver or renal impairments show little or no modification of pharmacokinetic parameters.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 source (direct Gemma or distilled Codex), 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".