Evaluation of the Pharmacokinetics of Metformin Following Coadministration With Doravirine in Healthy Volunteers
Bibliographic record
Abstract
Abstract Doravirine is a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type‐1 (HIV‐1) infection. In vitro and clinical data suggest that doravirine is unlikely to cause significant drug–drug interactions via major drug‐metabolizing enzymes or transporters. As a common HIV‐1 infection comorbidity, type 2 diabetes mellitus is often treated with metformin. Perturbations of metformin absorption or elimination may affect its safety and efficacy profile; therefore, understanding potential drug–drug interactions between doravirine and metformin is important. An open‐label, fixed‐sequence, 2‐period trial in healthy adults was conducted. Single‐dose metformin 1000 mg was administered in period 1; in period 2, doravirine 100 mg was administered once daily on days 1 to 7, and single‐dose metformin 1000 mg was administered on day 5. Plasma pharmacokinetics for metformin alone and coadministered with doravirine were assessed. Fourteen participants enrolled and completed the trial. Least‐squares geometric mean ratios and 90% confidence intervals of metformin AUC 0‐∞ , and C max following coadministration of metformin and doravirine compared with metformin alone were 0.94 (0.88‐1.00) and 0.94 (0.86‐1.03), respectively; metformin T max and half‐life were also minimally impacted. These data indicate that doravirine did not have a clinically relevant effect on the pharmacokinetics of metformin. Metformin alone and coadministered with doravirine was generally well tolerated. These data support coadministration of doravirine 100 mg and metformin 1000 mg without dose adjustment.
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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 | 0.005 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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 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".