Component
Ketoconazole
Ketoconazole. Species, exposure and limitations are retained in each linked claim.
1 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
Where it participates (unsigned role)
Formation of the major circulating metabolite in human liver microsomes had a Michaelis constant of 14.4 micromolar, of the chemical inhibitors screened only ketoconazole showed detectable inhibition, biotransformation was inhibited by ketoconazole and ritonavir with half-maximal concentrations below 0.02 micromolar, and using microsomes containing cDNA-expressed cytochromes the reaction was mediated by CYP3A4, CYP2C9, CYP2C19 and CYP2D6 with estimated relative contributions to net intrinsic clearance of 79% for CYP3A4 and 20% for CYP2C9 and less than 2% for the other two.
Experimental context and source evidence
- availability_state
- machinery_impairment Imported condition classification; unverified.
- evidence_span
- {"source_cache": "artifacts/sildenafil-research/10725306.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21d73da8afc20cb90f2aa2d9bafe7bdbefd7d07037ffb493681414b09154f6d6", "start_char": 0, "end_char": 1190, "text_sha256": "21d73da8afc20cb90f2aa2d9bafe7bdbefd7d07037ffb493681414b09154f6d6"}
- experimental_model
- In vitro biotransformation in human liver microsomes and microsomes containing heterologously expressed cytochromes
- exposure
- Formation of the major circulating metabolite with chemical inhibitors and cDNA-expressed cytochromes
- limitations
- Assigns the clearance quantitatively across cytochromes and identifies the inhibitors that matter. In vitro microsomes.
- nutrient_topic
- Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
- organism
- Human
- plain_language
- Four fifths of the clearance runs through one enzyme, so anything blocking that enzyme raises the level of the drug.
- primary_references
- [sil-p10725306] In vitro biotransformation of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. (2000). https://pubmed.ncbi.nlm.nih.gov/10725306/ DOI: 10.1016/s0090-9556(24)15055-6
- tissue_or_cell_type
- Liver microsomes
- trigger_kind
- machinery_impairment Imported condition classification; unverified.
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · In vitro biotransformation in human liver microsomes and microsomes containing heterologously expressed cytochromes · source_derived_draft · unverified_draft
### sil-cyp3a4-carries-the-clearance Formation of the major circulating metabolite in human liver microsomes had a Michaelis constant of 14.4 micromolar, of the chemical inhibitors screened only ketoconazole showed detectable inhibition, biotransformation was inhibited by ketoconazole and ritonavir with half-maximal concentrations below 0.02 micromolar, and using microsomes containing cDNA-expressed cytochromes the reaction was mediated by CYP3A4, CYP2C9, CYP2C19 and CYP2D6 with estimated relative contributions to net intrinsic clearance of 79% for CYP3A4 and 20% for CYP2C9 and less than 2% for the other two. Condition category: machinery_impairment nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: Four fifths of the clearance runs through one enzyme, so anything blocking that enzyme raises the level of the drug. organism: Human tissue_or_cell_type: Liver microsomes experimental_model: In vitro biotransformation in human liver microsomes and microsomes containing heterologously expressed cytochromes limitations: Assigns the clearance quantitatively across cytochromes and identifies the inhibitors that matter. In vitro microsomes. exposure: Formation of the major circulating metabolite with chemical inhibitors and cDNA-expressed cytochromes evidence_span: {"source_cache": "artifacts/sildenafil-research/10725306.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "21d73da8afc20cb90f2aa2d9bafe7bdbefd7d07037ffb493681414b09154f6d6", "start_char": 0, "end_char": 1190, "text_sha256": "21d73da8afc20cb90f2aa2d9bafe7bdbefd7d07037ffb493681414b09154f6d6"} [sil-p10725306] In vitro biotransformation of sildenafil (Viagra): identification of human cytochromes and potential drug interactions. (2000). https://pubmed.ncbi.nlm.nih.gov/10725306/ DOI: 10.1016/s0090-9556(24)15055-6
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.