Pharmacokinetics and Pharmacodynamics of Faldaprevir Following Multiple Oral Rising Doses in Healthy Volunteers and Subjects with Gilbert's Syndrome
Bibliographic record
Abstract
Abstract Faldaprevir (FDV) is an investigational NS3/NS4A protease inhibitor for chronic hepatitis C. This study evaluated the safety, tolerability, and pharmacokinetics (PK) of FDV after multiple rising doses in healthy male volunteers and subjects with Gilbert syndrome (GS). In this randomized, double‐blind, placebo‐controlled study, healthy males received once‐daily oral FDV (20, 48, 120 mg [ n = 6 per group], 240 mg [ n = 5]), or placebo ( n = 7). A single dose was given on Day 1, followed by a 72‐h washout and 21 days of dosing from day 4. Separately, 9 GS subjects received open‐label FDV 240 mg daily for 28 days. PK was assessed after the first and last doses; safety was evaluated throughout. FDV showed greater than dose‐proportional increases in exposure (gMean C max,ss : 99–5360 ng/mL; AUC τ ,ss : 1740–50,100 h·ng/mL) and time‐dependent PK with a linearity index >1. Mean t 1/2 was 20–30 h; steady state was reached in 6–7 days with an accumulation ratio of 2.8–3.1. FDV exposure in GS subjects was similar but slightly lower. Total bilirubin increased dose‐dependently, with higher indirect bilirubin in GS subjects. FDV exhibited non‐linear, time‐dependent PK and was generally well tolerated up to 240 mg/day in subjects with or without GS.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 | 0.001 |
| 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".