In vitro investigation of the hepatic extraction of RSD1070, a novel antiarrhythmic compound.
Bibliographic record
Abstract
PURPOSE: The hepatic extraction of a novel antiarrhythmic, RSD1070, was investigated to test the hypothesis that the poor bioavailability observed in rats is due to high hepatic metabolism. METHODS: The pharmacokinetics of RSD1070 was examined in rats (n=8) and its metabolism was investigated using pooled rat hepatic microsomes. The free fraction in plasma and microsomal matrices was determined by equilibrium dialysis. Hepatic extraction was predicted by scaling-up of the microsomal kinetic data using the well-stirred liver model. RESULTS: RSD1070 demonstrated tri-exponential decay following single iv bolus administration of a dose of 12 mg/kg. RSD1070 exhibited a rapid elimination, t1/2 of 25 +/- 8 min and a CL(tot) of 71 +/- 9 mL/min/kg. Renal clearance based on 24 h urinary recovery was determined to be insignificant (<< 1% of CL(tot)). A Michaelis-Menten model described the elimination of RSD1070 with a K(m) of 0.45 microg/mL and Vmax of 2.81 microg/min/mg microsomal protein. Taking the V(max)/K(m) ratio (CL(int)) as the basis for scaling, the data from the microsomal kinetic studies (75 mL/min/kg) closely approximated the apparent CL(tot). In the scale-up of the in vitro CL(int), plasma free fraction (1.5%) and microsomal free fraction (15%) were determined and incorporated into the well-stirred liver model. CONCLUSION: RSD1070 is a high hepatic extraction compound (E = 0.94) with a predicted CL(h) value that accounted for the CL(tot) observed in rats.
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 | 0.000 | 0.000 |
| 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".