Biopharmaceutical Characteristics of Nifurtimox Tablets for Age‐ and Body Weight‐Adjusted Dosing in Patients With Chagas Disease
Bibliographic record
Abstract
Treatment of Chagas disease with nifurtimox requires age- and body weight-adjusted dosing, resulting in complex dosing instructions. Appropriate formulations are needed for precise and compliant dosing, especially in pediatric patients. We characterized the biopharmaceutical features of a standard nifurtimox 120-mg tablet and a 30-mg tablet developed to improve dose accuracy. Two open-label, randomized crossover studies were conducted in adult outpatients with Chagas disease. One study investigated whether 4 × 30-mg tablets and 1 × 120-mg tablet were bioequivalent and whether tablets can be administered as an aqueous slurry without affecting bioavailability. The second study investigated the effect of a high-calorie/high-fat diet versus fasting on the absorption of nifurtimox after a single 4 × 30-mg dose. Interventions were equivalent if the 90% confidence interval (CI) of their least-squares (LS) mean ratios for both AUC0-tlast and Cmax were in the range of 80%-125%. The 4 × 30-mg and 1 × 120-mg tablet doses were bioequivalent (AUC0-tlast : LS mean ratio, 104.7%; 90%CI, 99.1%-110.7%; Cmax : LS mean ratio, 101.7%; 90%CI, 89.4%-115.6%; n = 24). Exposure when giving the 4 × 30-mg dose as a slurry or as tablets was comparable, with an AUC0-tlast ratio of 93.2% (84.2%-103.1%; n = 12) and a slightly decreased Cmax ratio for the slurry of 76.5% (68.8%-85.1%). Food improved the bioavailability of nifurtimox substantially (AUC0-tlast ratiofed/fasted , 172%; 90%CI, 154%-192%; Cmax ratiofed/fasted , 168%; 90%CI, 150%-187%). The data indicate that the 30- and 120-mg tablets are suitable for dosing adult and pediatric patients accurately; nifurtimox should be administered under fed conditions.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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) | 0.000 | 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".