Pharmacokinetics and Pharmacodynamics of Hyaluronan Infused into Healthy Human Volunteers
Bibliographic record
Abstract
The pharmacodynamics and elimination kinetics of escalating doses (1.5-12 mg/kg) of hyaluronan (HA) infusions were studied in healthy human volunteers.Metabolic breakdown of serum HA and associated adverse events were monitored throughout the study.The HA-binding capacities of circulating CD4+ and CD8+ T lymphocytes, CD19+ Blymphocytes and CD14+ peripheral blood monocytes (PBMC) were also quantified.Breakdown of infused HA into small fragments (<37 kDa) were not detected and adverse events related to HA infusions were infrequent and non-serious in nature.Binding of FITC-HA was greatest to CD14+ monocytes and the binding capacity of these cells for FITC-HA was significantly increased by the final HA infusion.At that time, binding to CD14+ monocytes was related to serum HA levels suggesting a close relationship between PK and PD of serum HA.Drug level analysis demonstrated a disproportional increase in the area under the serum concentration vs. time curve with increasing HA dose.The observed non-linear HA kinetics appears to result from a saturable elimination process as revealed by pharmacokinetic modeling.These results have implications for the use of injected HA for drug delivery or in imaging applications.
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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 | 0.001 |
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".