Potential Mechanisms by Which Peceol® Increases the Gastrointestinal Absorption of Amphotericin B
Bibliographic record
Abstract
PURPOSE: The purpose of this study was to ascertain how the incorporation of AmpB into a glyceride-rich excipient Peceol significantly increased Amphotericin B's (AmpB) gastrointestinal absorption in white male Sprague-Dawley rats. Based on preliminary studies, our working hypothesis was that incorporation of AmpB into mixed micelles composed of Peceol would significantly enhance gastro-intestinal (GI) tract absorption by increasing lymphatic drug transport and decreasing P-glycoprotein (PGP)-mediated drug efflux. METHODS: I. Lymphatic Transport STUDIES: Following an overnight fast (12-16 hr) and 48 hr postsurgery, rats were divided into two treatment groups and received a single-dose oral gavage (1 mL total volume) at 0700 h of either desoxycholate (DOC)-AmpB (5 mg AmpB/kg; n = 6 at each time point) or AmpB incorporated into 100% Peceol (Peceol-AmpB; 5 mg AmpB/kg; n = 6 at each time point). Mesenteric lymph samples were obtained prior to and at 0-4-hr, 4-6-hr, and 6-8-hr intervals post oral gavage. An equal volume of normal saline (1 mL) was administered intravenously to the animal following each blood draw to prevent fluid depletion throughout the duration of the study. Lymph was immediately harvested by centrifugation and analyzed for drug by high-performance liquid chromatography (HPLC). II. Multidrug Resistance 1 (mdr-1) STUDIES: Caco-2 cells were seeded at 10,000 cells/cm2 in T-75 flasks. When the cells reached 80% confluency, they were treated for 1 day and 7 days with 0.1% to 1.0% (v/v) Peceol or media alone (control). Following treatment, total RNA was isolated using TRIzol reagent, followed by reverse transcription into single-stranded cDNA. Polymerase chain reactions (PCR) were performed with specific primers for mdr-1. The PGP protein was determined by Western Blot Analysis. RESULTS: Mean weight of rats was not significantly different prior to and following drug administration. Similarly, kidney, liver, lung, spleen, and heart weights were not different between DOC-AmpB and Peceol-AmpB treatment group. A significantly greater amount of AmpB was transported through the mesenteric lymph duct for all the time intervals used following the administration of Peceol-AmpB treatment group compared to the administration of DOC-AmpB (suspension). A significant lower mdr-1 mRNA and PGP protein expression within Caco-2 cells was observed following 1 and 7 days treatment with Peceol 0.1% to 1.0% (v/v) compared to nontreated controls. CONCLUSIONS: Taken together, these findings suggest that Peceol increases the gastrointestinal absorption of AmpB by increasing the amount of drug that is transported through the mesenteric lymph duct and by decreasing mdr-1 mRNA and PGP protein expression, resulting in lower PGP-mediated AmpB efflux.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".