Impact of Transporter Polymorphisms on Drug Development: Is It Clinically Significant?
Bibliographic record
Abstract
Drug transporters are becoming increasingly recognized as relevant to the drug development process. This may be a reflection of increasing target complexity and the need for high-affinity interaction with drug targets that minimize off-target side effects. Moreover, as new molecular entities (NMEs) become larger in size and amphipathic in nature, interaction with drug transporters, both uptake as well as efflux, becomes increasingly likely. In some cases transporters may limit the absorption or organ-specific entry of NMEs, whereas in other cases transporters may enhance their absorption or tissue accumulation. Indeed, in some cases, transporters may prove to be a therapeutic target. Accordingly, a better understanding of potentially clinically relevant drug transporter polymorphisms earlier in the drug development process is highly desirable. In this review we examine key transporters that are important to the absorption, distribution, and excretion of a large number of drugs in clinical use. Importantly, we provide our assessment of the potential impact of known polymorphisms in such transporters and discuss whether there is sufficient evidence to incorporate these polymorphisms in the drug development process.
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How this classification was reachedexpand
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 | 0.007 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.006 | 0.004 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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 teacher head, 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".