Pharmacodynamic effects of molidustat on erythropoiesis in healthy cats
Bibliographic record
Abstract
BACKGROUND: Inhibition of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) stimulates erythropoiesis in rats, dogs, monkeys, and humans. HYPOTHESIS/OBJECTIVE: Determine if molidustat, a novel HIF-PH inhibitor, stimulates erythropoiesis in healthy cats. ANIMALS: Seventeen healthy adult laboratory cats. METHODS: Randomized, placebo-controlled study. Cats were treated PO once daily with suspensions of 0 (Group 1; n = 6), 5 (Group 2; n = 6), or 10 (Group 3; n = 5) mg/kg of molidustat. Effects on red blood cell parameters, reticulocyte indices and plasma erythropoietin (EPO) concentrations were evaluated. Molidustat treatment was stopped when hematocrit (HCT) exceeded 60%. RESULTS: Compared to placebo, a significant increase in mean HCT was evident starting on Day 14 (Group 2:54.4% vs 40.3%, P < .001, 95% confidence interval [CI] for the difference [8.95-19.28]; Group 3:61.2% vs 40.3%, P < .001, 95% CI [15.48-26.43]) and remained significantly higher for the entire treatment period. In molidustat-treated groups, HCT exceeded 60% on Day 21 (Group 2) and Day 14 (Group 3). Mean HCT in molidustat-treated cats returned to within the reference range (29%-45%) after Day 56 and was numerically comparable to placebo from Day 70 onwards. Red blood cell count and hemoglobin concentrations followed a similar pattern as HCT. Mean EPO concentrations significantly increased after molidustat administration on all assessment days. Molidustat treatments were well tolerated. CONCLUSIONS AND CLINICAL IMPORTANCE: Marked erythropoietic effects were identified after daily administration of molidustat to healthy cats and additional studies are warranted to evaluate the effects in anemic cats.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 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".