The effect of increased lipoprotein levels on the pharmacokinetics of ketoconazole enantiomers in the rat
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
(±)-Ketoconazole (KTZ) is a chiral antifungal drug that inhibits cytochrome P450 (CYP)-mediated metabolism of other drugs. Because of its lipophilicity, KTZ pharmacokinetics might change in elevated plasma lipoprotein concentrations. To explore that, the stereoselective pharmacokinetics of KTZ were assessed in a rodent model of hyperlipidaemia (HL). Rats were given KTZ intravenously (i.v.) or orally. Serial blood samples were collected over 24 h for the iv dosed groups. After oral doses, plasma and liver specimens were obtained up to 6 h after dosing. All specimens were assayed using stereospecific assay. Orally and iv dosed rats showed no significant differences between normolipidemic and hyperlipidaemic area under the plasma concentrations vs. time curves or clearance (CL), of both KTZ enantiomers. In iv dosed rats, however, the volume of distribution (V(ss)) was significantly higher in HL for both enantiomers. The (+):(-) KTZ ratios of CL and V(ss) were also higher in hyperlipidaemic rats. After oral doses, the liver to plasma concentration ratios of (-)-KTZ (but not antipode) were significantly lower in HL. In conclusion, HL caused an increase in V(ss), and possibly decreased liver uptake of the more potent CYP-inhibiting (-) enantiomer.
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.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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 it