Assessing the plasma pharmacokinetics, tissue distribution, excretion and effects on cholesterol pharmacokinetics of a novel hydrophilic compound, FM-VP4, following administration to rats.
Bibliographic record
Abstract
PURPOSE: The purpose of this project was to 1) assess the disposition kinetics of [3H]-cholesterol following co-administration with a novel hydrophilic compound, FM-VP4, and 2) determine the pharmacokinetics, tissue distribution and excretion of [3H]FM-VP4 following single oral (150 mg/kg which includes 100 mCi of radiolabel) and intravenous (15 mg/kg which includes 10 mCi of radiolabel) doses. METHODS: Following an overnight fast (12-16 h) and 48 h post-surgery, adult male Sprague Dawley rats were divided into six treatment groups (n=4/group). Groups received single oral doses of 25 mCi/ml [3H]cholesterol alone or with 5, 10, 20, 50 and 100 mg/kg FM-VP4 at 0700 h. Ten percent Intralipid was used to solubilize and co-administer [3H]-cholesterol and FM-VP4. LC-MS analysis confirmed minimal cholesterol and vegetable stanol content within 10% Intralipid. Thin layer chromatography was used to confirm that the majority of radioactivity measured in plasma was associated with either esterified or unesterified cholesterol. In a second study pharmacokinetics of [3H]FM-VP4 were studied following intravenous or orally gavaged doses (n=8). Tissues, urine and feces were also collected in FM-VP4 kinetics study to measure tissue distribution of radioactivity. Plasma [3H]-cholesterol and [3H]FM-VP4 were tested for radioactivity. RESULTS: FM-VP4 co-administration significantly decreased [3H]-cholesterol AUC0-48h and Cmax, and increased CL/F and Vd/F of [3H]-cholesterol as compared to controls in a dose-dependent manner. Following oral administration of [3H]FM-VP4, the majority of radioactivity following was recovered in the feces and gastrointestinal (GI) tract. The compound exhibited an oral bioavailability of 6.5%. Following IV administration, a two-compartment pharmacokinetic model was observed and the majority of the radioactivity was recovered in the GI tract. CONCLUSIONS: FM-VP4 reduces plasma concentration of [3H]-cholesterol in fasting rats. [3H]FM-VP4 has a very low oral bioavailability.
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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) | 0.001 | 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".