Influence of Controlled Rheumatoid Arthritis on the Action and Disposition of Verapamil: Focus on Infliximab
Bibliographic record
Abstract
Active rheumatoid arthritis (RA), obesity, and old age are associated with reduced responsiveness to the calcium channel antagonist verapamil despite increased drug concentrations. The diminishing effect appears to be associated with the severity of inflammation. We examined pharmacodynamics and pharmacokinetics of verapamil in patients with controlled RA. Volunteers included RA patients in remission: 12 on infliximab, 8 on other antirheumatic therapy, and 12 healthy subjects. Verapamil plasma concentrations and selected inflammatory mediators as well as blood pressure and electrocardiographic parameters were recorded after a single 80-mg dose of verapamil. Inflammatory mediators were all below what is reported for active RA, confirming that RA was controlled. The tumor necrosis factor-alpha concentration, however, was significantly higher in the infliximab group compared with other groups and the literature value for active RA. No significant difference was observed between groups in terms of percentage prolongation of PR interval despite a trend toward a lower response in the RA groups, the mean plasma concentrations, and the total and unbound area under the curve of verapamil. However, the slope of the S-verapamil concentration-effect curve was steeper for controls compared with the RA patients. Remission from active disease appears to restore plasma protein levels and hepatic drug metabolism activity in patients with RA, resulting in relatively normal verapamil pharmacokinetics.
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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 | 0.004 | 0.002 |
| 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 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".