Effects of physiological covariables on pharmacokinetic parameters of clomipramine in a large population of cats after a single oral administration
Bibliographic record
Abstract
This study was conducted to confirm an interindividual variability in pharmacokinetic parameters of clomipramine in a large population of cats and to identify potential covariables that would explain the presence of such pharmacokinetic variability after a single dose of Clomicalm. Clomipramine hydrochloride was administered orally according to a weight-dose chart from 0.32 to 0.61 mg/kg, to 76 cats and five blood samples were then taken by direct venipuncture at 1, 3, 6, 12, and 24 h. Plasma concentrations of clomipramine and desmethylclomipramine (DCMP) were measured by LC-MS/MS. The Standard Two-Stage technique was used to assess differences and detect correlations between pharmacokinetic parameter estimates and individual covariables. A large interindividual variability in all pharmacokinetic parameters (CV% 64-124) was detected. Statistically significant gender-related differences were detected in MR and Cl/F, where female cats had a higher mean MR (0.53) and faster Cl/F (0.36 L/h.kg) than males (0.36 and 0.21 L/h.kg, respectively). No correlation could be found between clomipramine AUC0-24 h or DCMP AUC0-24 h and sedation scores. Further feline studies are required to assess these findings after multiple dosing of clomipramine and DCMP to allow clinical extrapolation.
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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) | 0.001 | 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) | 0.000 | 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 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".