Development of an Oral Amphotericin B Formulation as an Alternative Approach to Parenteral Amphotericin B Administration in the Treatment of Blood-Borne Fungal Infections
Bibliographic record
Abstract
In the Fall of 1999, we presented at medical "Grand Rounds" to a number of Infectious Diseases physicians at Vancouver General Hospital about the co-administration of several antifungal compounds in the treatment of blood-borne fungal infections to patients who were immunocompromised (i.e. cancer patients, patients waiting organ transplantation, HIV/AIDs patients, etc.). During the presentation, a physician from the back of the room called out "can you develop an oral formulation of amphotericin B which could be effective and not have the side-effects associated with the parenteral formulations of the drug". The physician stated that an oral formulation would be a big step forward, improving patient compliance, helping in pre-treatment without admitting patients to the hospital prior to organ transplantation and it would be cost-effective. Initially, I responded to the physician, that it would not be possible to develop an oral amphotericin B formulation that could be absorbed from the gastrointestinal (GI) tract in a high enough concentration to be effective in treating blood-borne fungal infections and yet remains non-toxic due to the physical chemical properties of the drug. However, as I travelled back to my lab from the meeting, it struck me that our understanding of how lipids had been processed and orally absorbed from the GI had advanced to the point the maybe incorporating amphotericin B into such lipids might work. Within several years, our laboratory was able to develop a novel oral amphotericin B formulation that was indeed effective in treating systemic fungal infections without the side-effects associated with the drug in a variety of fungal animal models.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".