The effect of increased lipoprotein levels on the pharmacokinetics of cyclosporine A in the laboratory rat
Why this work is in the frame
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Bibliographic record
Abstract
The response of cyclosporine A (CyA) blood concentrations following changes in lipoprotein levels have been inconsistent. Some studies show increases in concentrations, whereas others have shown decreases. The intent of this study was to examine the effect of two rat models of increased lipoprotein on the pharmacokinetics of CyA. One was a simulated high fat content meal, in which 1% cholesterol in peanut oil was administered. The other was the poloxamer 407-induced model of hyperlipidemia. Rats in these two groups were compared to a group fasted overnight before the study. In rats given a simulated high fat meal, at most time points the mean blood and plasma concentrations were lower, though not significantly, compared to fasted animals. Oral lipid led to no significant changes in the measured pharmacokinetic parameters of blood or plasma area under the concentration vs time curve (AUC), clearance (CL), volume of distribution (Vd) or plasma unbound fraction. In the poloxamer 407-treated hyperlipidemic rats there were significant reductions in plasma unbound fraction plasma, Vd and terminal half-life, but not AUC or CL, compared to normolipidemic rats. In contrast, the CL, Vd and t1/2 in the oral lipid-fed rats were all significantly higher than the poloxamer 407 treated animals. Oral absolute bioavailability of CyA was unchanged by oral lipid. In humans and rats the pharmacokinetics of CyA in the face of increased lipoprotein levels do not correspond well to what is typically seen for other drugs that are known to bind to lipoproteins.
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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 | 0.001 | 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) | 0.000 | 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 it