Comparative pharmacokinetics, tissue distribution and excretion of free versus liposomal vincristine in rats.
Bibliographic record
Abstract
2041 Vincristine sulfate is a cell-cycle specific anti-mitotic agent used in the treatment of Non-Hodgkins Lymphoma. Its encapsulation into liposomes extends the systemic circulation of the drug and mediates prolonged exposure of the drug to tumour sites. Prolonged exposure of cell-cycle specific anti-mitotic drugs such as vincristine would benefit from liposomal drug delivery. Vincristine Sulfate Liposomes Injection (VSLI) is vincristine encapsulated in sphingomyelin/ cholesterol liposomes. In these studies, a single iv bolus dose of VSLI or VCR was administered to Sprague-Dawley rats at 2.0 mg/m2. Blood, tissues, urine and bile/feces samples were collected at specific time points and analyzed by LSC. Following VSLI administration, total vincristine concentrations in plasma exhibits mono-exponential decline whereas the corresponding profile in VCR-treated rats exhibit bi-exponential decline with a rapid initial phase followed by a slower elimination phase. The volume of distribution and clearance of total vincristine in VSLI-treated rats was significantly less than that of the free drug resulting in radically greater AUC. Tissue distribution data show that liposomal vincristine accumulated preferentially in tissues of the RES (e.g., liver, spleen) as demonstrated by higher tissue AUC in VSLI-treated rats. Despite the differences in plasma PK and tissue distribution in VSLI- vs VCR-treated rats, the major route of vincristine elimination is the same (i.e. biliary excretion); however vincristine excretion was delayed in VSLI-treated rats. In conclusion, VSLI increases circulation longevity of vincristine and causes preferential accumulation of liposomal drug in tissues with permeable vasculature including tumour.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".