Pharmacokinetics of mirodenafil, a new erectogenic, and its metabolite, SK3541, in rats: involvement of CYP1A1/2, 2B1/2, 2D subfamily, and 3A1/2 for the metabolism of both mirodenafil and SK3541
Bibliographic record
Abstract
PURPOSE: This study was performed to find which types of hepatic CYP isoforms are responsible for the metabolism of mirodenafil (a new erectogenic) and one of its metabolite, SK3541, using various hepatic CYP inducers and inhibitors in rats. METHODS: Mirodenafil at a dose of 20 mg/kg was administered intravenously to control rats and rats pretreated with various CYP inducers and inhibitors. The disappearance of SK3541 was also measured in vitro hepatic microsomes of rats with and without CYP inducer and inhibitors. RESULTS: Compared to controls, in rats pretreated with 3-methylcholanthrene, orphenadrine, and dexamethasone (main inducers of CYP1A1/2, 2B1/2, and 3A1/2, respectively), the non-renal clearances (CLNRs) of mirodenafil were significantly faster (by 39.4%, 59.3%, and 63.9%, respectively). However, compared to controls, in rats pretreated with quinine and troleandomycin (main inhibitors of CYP2D subfamily and 3A1/2, respectively), the CLNRs of mirodenafil were significantly slower (by 36.1% and 33.2%, respectively). In rat hepatic microsomes spiked with furafylline, quinine, and troleandomycin (main inhibitors of CYP1A2, 2D subfamily, and 3A1/2, respectively), the intrinsic clearances (CLints) for the disappearance of SK3541 were significantly slower (by 18.4%, 35.3%, and 51.5%, respectively) than controls. Also in rat hepatic microsomes pretreated with orphenadrine (a main inducer of CYP2B1/2), the CLint for the disappearance of SK3541 was significantly faster (by 55.5%) than controls. CONCLUSIONS: The above data suggest that hepatic CYP1A1/2, 2B1/2, 2D subfamily, and 3A1/2 are involved in the metabolism of both mirodenafil and SK3541 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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".