Oxidative activation of linezolid to a reactive species: Implications for linezolid adverse drug reactions
Bibliographic record
Abstract
Background Linezolid is a novel oxazolidone antimicrobial agent which is effective against gram positive bacteria. It is extensively metabolized. Serious adverse drug reactions to linezolid occur relatively frequently and can be life threatening. The mechanism of these and the potential role of metabolites is not known. Methods Linezolid was incubated in increasing concentrations and over increasing incubation times with Jurkat e6.1 lymphoblasts in the presence and absence of a murine microsomal activating system or a horseradish-peroxidase (HRP) activating system. Viability was determined after incubation using a tetrazolium-based assay. Results No toxicity was demonstrated with linezolid over a concentration range from 0 to 1200 μM in the absence of murine microsomes. In contrast, concentration-dependent toxicity was demonstrated when cells were incubated in the presence of the HRP system (100±5% viability at 0μM, 20± 3% viability at 625 μM, p<0.05). At concentrations greater than 1000 μM, cell viability increased back towards baseline (80±5% at 1250 μM, p<0.05). Conclusion Oxidative activation of linezolid appears to produce metabolite(s) toxic to lymphoblasts not dependent on CYP450-dependent metabolism. At high concentrations linezolid may act as an anti-oxidant. This suggests that reactive linezolid metabolites may play a role in linezolid-related adverse drug reactions. Clinical Pharmacology & Therapeutics (2005) 77, P69–P69; doi: 10.1016/j.clpt.2004.12.157
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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".