Evaluation of the Pharmacokinetic Interaction Between Doravirine and Methadone
Bibliographic record
Abstract
Doravirine is a novel nonnucleoside reverse transcriptase inhibitor indicated for the treatment of HIV type 1 infection. A subset of people living with HIV receives methadone for the treatment of opioid addiction. The current study (NCT02715700) was an open-label, multiple-dose, drug interaction study in participants on a methadone maintenance program to investigate potential drug-drug interactions between doravirine and methadone. Participants received a stable methadone maintenance dose of 20 to 180 mg once daily for 14 days prior to day 1 and remained on their maintenance dose over days 1 through 7. On days 2 through 6, an oral dose of doravirine 100 mg was coadministered. For doravirine and methadone pharmacokinetic analysis, blood samples were collected before dosing through 24 hours after dosing. Fourteen participants were enrolled; all participants completed the study. For R-methadone, geometric least squares mean ratios (90% confidence intervals) for dose-normalized area under the plasma concentration-time curve from time zero to 24 hours, plasma concentration at 24 hours, and maximum plasma concentration ([methadone + doravirine]/methadone alone) were 0.95 (0.90-1.01), 0.95 (0.88-1.03), and 0.98 (0.93-1.03), respectively. For doravirine, based on a comparison with historical data, modest decreases in area under the plasma concentration-time curve from time zero to 24 hours, plasma concentration at 24 hours, and maximum plasma concentration were observed after coadministration of doravirine and methadone; geometric least squares mean ratios ([methadone + doravirine]/doravirine alone [90% confidence intervals]) were 0.74 (0.61-0.90), 0.80 (0.63-1.03), and 0.76 (0.63-0.91), respectively. Coadministration of doravirine and methadone was generally well tolerated. No serious adverse events occurred, and there were no discontinuations. In conclusion, coadministration of methadone and doravirine did not have a clinically meaningful effect on the pharmacokinetic profile of either agent.
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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 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.001 | 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".