Correlation-based prediction of tissue-to-plasma partition coefficients using readily available input parameters
Bibliographic record
Abstract
UNLABELLED: 1. RATIONALE: Tissue-to-plasma partition coefficients (Kp) that characterize the tissue distribution of a drug are important input parameters in physiologically based pharmacokinetic (PBPK) models. The aim of this study was to develop an empirically derived Kp prediction algorithm using input parameters that are available early in the investigation of a compound. 2. METHODS: The algorithm development dataset (n = 97 compounds) was divided according to acidic/basic properties. Using multiple stepwise regression, the experimentally derived Kp values were correlated with the rat volume of distribution at steady state (Vss) and one or more physicochemical parameters (e.g. lipophilicity, degree of ionization and protein binding) to account for inter-organ variability of tissue distribution. 3. RESULTS: Prediction equations for the value of Kp were developed for 11 tissues. Validation of this model using a test dataset (n = 20 compounds) demonstrated that 65% of the predicted Kp values were within a two-fold error deviation from the experimental values. The developed algorithms had greater prediction accuracy compared to an existing empirically derived and a mechanistic tissue-composition algorithm. 4. CONCLUSIONS: This innovative method uses readily available input parameters with reasonable prediction accuracy and will thus enhance both the usability and the confidence in the outputs of PBPK models.
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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 | 0.002 | 0.011 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".