Safety and pharmacokinetics of a kinin B1 receptor peptide agonist produced with different counter-ions
Bibliographic record
Abstract
Several studies have shown the potential therapeutic utility of kinin B1 receptor (B1R) peptide agonists in neurological and ischemic cardiovascular diseases and brain cancer. Preclinical safety studies are a prerequisite for further drug development. The objectives of this study were to determine the acute toxicity and pharmacokinetics of the peptide B1R agonist, SarLys[dPhe8]desArg9-bradykinin (NG29), as trifluoroacetate (TFacetate) or acetate salt form, following intravenous injection in rats. A maximum tolerated dose (MTD) of NG29-TFacetate was established at 75 mg/kg from the results of a dose range-finding study (up to 200 mg/kg). The short-term (4-day) repeat-dose toxicity study of NG29, using its MTD value, showed that NG29-acetate exhibited minimal non-adverse clinical pathology changes in hematology, coagulation, clinical chemistry and urine parameters and severe kidney histopathological changes characterized by renal tubular degeneration. No such effects were observed with NG29-TFacetate. At the injection site, NG29-TFacetate was considered to be more locally irritating when compared to the acetate form. The extent of exposure and half-life values of NG29-TFacetate were comparable to the acetate form (AUC0-α of 10.2 mg/l*h vs. 9.9 mg/l*h; T1/2 of 2.3 h vs. 2.4 h). This study shows that in rats NG29-TFacetate exhibits a superior tolerability profile compared with the peptide acetate form.
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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) | 0.000 | 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".