The stereoselective pharmacokinetics of bupivacaine after racemate, and the effects of high-fat diet and sex in Sprague–Dawley rats
Bibliographic record
Abstract
OBJECTIVES: The primary aim was to characterize the influence of diet-induced obesity on the stereoselective pharmacokinetics of racemic bupivacaine in male and female rats. METHOD: Rats were fed either a standard diet (StdD) or high-fat diet (HFD) for 12 weeks. A stereoselective assay was used to measure plasma concentrations after subcutaneous injection of racemic bupivacaine. A rich sampling protocol was initially employed for cannulated rats, while a sparse sampling in non-cannulated rats, coupled with Bayesian forecasting, was used in dietary assessment. KEY FINDINGS: Clearance (CL) of both enantiomers was significantly reduced in males fed HFD. StdD females had lower peak concentrations and longer elimination phases than StdD males. Stereoselectivity was modest, with the d-enantiomer displaying marginally higher CL than antipode. There was an apparent late-absorption peak with rich sampling. CONCLUSION: Bupivacaine exhibits modest stereoselectivity in rats, with diet and sex influencing CL. The application of Bayesian forecasting in sparse sampling models in rats proved to be a robust tool for pharmacokinetic assessment, aligning with the goals of reducing numbers, refining experimental design and replacing invasiveness of procedures in the use of animals.
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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 | 0.001 |
| 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".