Pharmacokinetics of desethylamiodarone in the rat after its administration as the preformed metabolite, and after administration of amiodarone
Bibliographic record
Abstract
The pharmacokinetics of desethylamiodarone (DEA), the active metabolite of amiodarone (AM), were studied in the rat after administration of AM or preformed metabolite. Rats received 10 mg/kg of either intravenous or oral AM HCl or DEA base. Blood samples were obtained via a surgically implanted jugular vein cannula. Plasma concentrations were measured by a validated LC/MS method. In all AM treated rats, AM plasma concentrations greatly exceeded those of the formed DEA. The fraction of AM converted to DEA after i.v. administration was 14%. Amiodarone had a significantly lower (approximately 50%) clearance than DEA, although the volume of distribution and terminal phase half-life did not differ significantly. The hepatic extraction ratio of DEA was 0.48, similar to that of AM (0.51). Oral AM demonstrated higher plasma AUC (5.6 fold) and higher C(max) (6.1 fold) than oral DEA and oral bioavailability of AM (46%) was greater than DEA (17%). The estimated fraction of the oral dose of AM converted to DEA was 4.5 fold higher than after i.v. administration, suggesting first-pass formation of DEA from AM. Amiodarone and DEA differed in their pharmacokinetic characteristics mostly due to a higher CL of DEA. With oral dosing, AM appeared to undergo significant presystemic first-pass metabolism within the intestinal tract.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| 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".