Pharmacokinetic modeling of tranexamic acid for patients undergoing cardiac surgery with normal renal function and model simulations for patients with renal impairment
Why this work is in the frame
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Bibliographic record
Abstract
Tranexamic acid (TXA), an effective anti-fibrinolytic agent that is cleared by glomerular filtration, is used widely for cardiopulmonary bypass (CPB) surgery. However, an effective dosing regimen has not been fully developed in patients with renal impairment. The aims of this study were to characterize the inter-patient variability associated with pharmacokinetic parameters and to recommend a new dosing adjustment based on the BART dosing regimen for CPB patients with chronic renal dysfunction (CRD). Recently published data on CPB patients with normal renal function (n = 15) were re-examined with a two-compartment model using the ADAPT5® and NONMEMVII® to identify covariates that explain inter-patient variability and to ascertain whether sampling strategies might affect parameter estimation. A series of simulations was performed to adjust the BART dosing regimen for CPB patients with renal impairment. Based on the two-compartmental model, the number of samples obtained after discontinuation of TXA infusion was found not to be critical in parameter estimation (p > 0.05). Both body weight and creatinine clearance were identified as significant covariates (p < 0.005). Simulations showed significantly higher than normal TXA concentrations in CRD patients who received the standard dosing regimen in the BART trial. Adjustment of the maintenance infusion rate based on the percent reduction in renal clearance resulted in predicted plasma TXA concentrations that were safe and therapeutic (~100 mg·L(-1) ). Our proposed dosing regimen, with consideration of renal function, is predicted to maintain effective target plasma concentrations below those associated with toxicity for patients with renal failure for CPB.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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 it