Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady‐state in healthy subjects
Why this work is in the frame
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Bibliographic record
Abstract
AIMS: To evaluate potential pharmacokinetic interactions between phenobarbitone and retigabine, a new antiepileptic drug. METHODS: Fifteen healthy men received 200 mg of retigabine on day 1. On days 4-32, phenobarbitone 90 mg was administered at 22.00 h. On days 26-32, increasing doses of retigabine were given to achieve a final dose of 200 mg every 8 h on day 32. The pharmacokinetics of retigabine were determined on days 1 and 32, and those for phenobarbitone on days 25 and 31. RESULTS: After administration of a single 200 mg dose, retigabine was rapidly absorbed and eliminated with a mean terminal half-life of 6.7 h, a mean AUC of 3936 ng x ml(-1) x h and a mean apparent clearance of 0.76 l x h(-1) x kg(-1). Similar exposure to the partially active acetylated metabolite (AWD21-360) of retigabine was observed. After administration of phenobarbitone dosed to steady-state, the pharmacokinetics of retigabine at steady-state were similar (AUC of 4433 ng x ml(-1) x h and t1/2 of 8.5 h) to those of retigabine alone. The AUC of phenobarbitone was 298 mg x l(-1) x h when administered alone and 311 mg x ml(-1) x h after retigabine administration. The geometric mean ratios and 90% confidence intervals of the AUC were 1.11 (0.97, 1.28) for retigabine, 1.01 (0.88, 1.06) for AWD21-360 and 1.04 (0.96, 1.11) for phenobarbitone. Individual and combined treatments were generally well tolerated. One subject was withdrawn from the study on day 10 due to severe abdominal pain. Headache was the most commonly reported adverse event. No clinically relevant changes were observed in the electrocardiograms, vital signs or laboratory measurements. CONCLUSIONS: There was no pharmacokinetic interaction between retigabine and phenobarbitone in healthy subjects. No dosage adjustment is likely to be necessary when retigabine and phenobarbitone are coadministered to patients.
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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 | 0.002 | 0.001 |
| 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 | 0.001 |
| 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