Stereoselective halofantrine and desbutylhalofantrine disposition in the rat: cardiac and plasma concentrations and plasma protein binding
Bibliographic record
Abstract
Halofantrine (HF) is a chiral antimalarial drug known to cause cardiac arrhythmias in susceptible patients. In this study, the cardiac uptake and plasma protein binding of HF and desbutylhalofantrine (DHF) enantiomers were examined in the rat. Rats were given 2 mg/kg of either HF HCl or DHF HCl intravenously, then sacrificed at various times after dosing. Specimens were assayed using stereospecific methods. Uptake of HF and DHF enantiomers into heart was rapid. Substantial concentrations of both HF and DHF enantiomers were observed in rat heart, with stereoselectivity being noted for both in plasma and heart. Stereoselectivity was more pronounced for HF (AUC (+):(-) ratio= 1.58) than DHF (AUC (+):(-) ratio =1.16) in heart tissue. Heart:plasma AUC ratios of 6.8-8.0, and 9.3-21, were observed for HF and DHF enantiomers, respectively, indicating that DHF has greater cardiac uptake than HF itself. Plasma protein binding was extensive for both HF and DHF (>99.95%), and was stereoselective for DHF, with a 38% higher unbound fraction for (-)-DHF than antipode. In contrast, binding of HF enantiomers was non-stereoselective. The lower degree of stereoselectivity for DHF in heart tissues was attributable to its greater stereoselectivity in plasma protein binding.
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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 | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".