Safety, Tolerability, and Pharmacokinetics of Single Oral Doses of BCH-10652 in Healthy Adult Males
Bibliographic record
Abstract
Racemic dOTC (BCH-10652) is a novel nucleoside reverse transcriptase inhibitor consisting of two enantiomers of 2'-deoxy-3'-oxa-4'-thiocytidine, (-)dOTC and (+)dOTC, that have both shown activity against human immunodeficiency virus type 1. The objectives of this study were to characterize the safety, tolerability, and stereospecific pharmacokinetics of single oral doses of racemic dOTC in healthy, nonsmoking adult male volunteers. Subjects received single oral doses of 100, 200, 400, 800, and 1,600 mg of racemic dOTC in a placebo-controlled, dose-rising, incomplete crossover study design, and the pharmacokinetics of both (+)dOTC and (-)dOTC were determined. At least six subjects were studied at each dose level, with each subject studied in three of five periods, receiving two different doses of racemic dOTC and one placebo dose. Plasma and urine drug concentrations were measured for 24 to 48 h after each dose. Pharmacokinetic models were fitted to the plasma concentrations of (+)dOTC and (-)dOTC using maximum likelihood and maximum a posteriori Bayesian procedures. Statistical hypothesis testing was by nonparametric analysis of variance (where possible) and, when tests with dose as a covariate were performed, by linear mixed-effects modeling. The mean terminal elimination half-lives for (+)dOTC and (-)dOTC were 15.3 h (coefficient of variation [CV], 28%) and 11.3 h (CV, 43%), respectively (P<0.05). The mean CV for total oral clearance (liter/h/65 kg) was 17.5 (25%) for (+)dOTC and 21.5 (24%) for (-)dOTC; for oral steady-state volume of distribution (liter/65 kg), values were 61.8 (24%) for (+)dOTC and 34.1 (33%) for (-)dOTC (P<0.05). The mean CV for renal clearance (liter/h/65 kg) of (+)dOTC was 10.4 (19%) and for (-)dOTC was 13.6 (20%) (P<0.05). There was no significant effect of dose size on the pharmacokinetics of racemic dOTC. All doses were well tolerated, and no serious adverse events or laboratory abnormalities were observed.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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 | 0.000 |
| 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".