About this pathway
Acenocoumarol is an anticoagulant which is administered as a racemic mixture. It exerts its clinical effect by inhibiting vitamin K epoxide reductase (VKORC1).
Around 90-99% of acenocoumarol clearance is through 6- and 7-hydroxylation of the parent drug, with the R-enantiomer more likely to undergo 6-hydroxylation and the S-enantiomer more likely to be 7-hydroxylated [Article:8220911]. Hydroxylation of S-acenocoumarol is principally mediated by CYP2C9 with a minor contribution from CYP2C18 and CYP2C19, while R-acenocoumarol hydroxylation is catalyzed by CYP2C9 and CYP2C19 [Articles:8220911, 11038154]. CYP1A2 also plays a role in 6-hydroxylation of R-acenocoumarol [Article:11038154].
8-hydroxylated metabolites of both R- and S-acenocoumarol have been identified in vitro, but their formation in human liver microsomes was found to be low. As a result, they are not shown in this figure [Article:11038154].
Variation in CYP2C9 has been associated with changes in patient response to acenocoumarol, including risk of overanticoagulation and time to stable INR [Article:15116052]. ClinPGx has several high-level clinical annotations for acenocoumarol and CYP2C9, which can be found here. Other studies have found associations between acenocoumarol dosage and variants in several genes, including CYP2C9, CYP2C18, CYP4F2 and VKORC1 [Articles:19578179, 29935043]. However, the clinical actionability of these associations is unclear, as the Dutch Pharmacogenetics Working Group (DPWG) has issued a ‘no recommendation’ for acenocoumarol and CYP2C9.
Reactions & interactions (13)
-
Biochemical Reaction
acenocoumarol → R-6-hydroxyacenocoumarol
-
Biochemical Reaction
acenocoumarol → R-7-hydroxyacenocoumarol
-
Biochemical Reaction
acenocoumarol → S-7-hydroxyacenocoumarol
-
Biochemical Reaction
acenocoumarol → S-6-hydroxyacenocoumarol
-
Catalysis
CYP2C9 → Biochemical Reaction
-
Catalysis
CYP1A2 → Biochemical Reaction
-
Catalysis
CYP2C19 → Biochemical Reaction
-
Catalysis
CYP2C19 → Biochemical Reaction
-
Catalysis
CYP2C9 → Biochemical Reaction
-
Catalysis
CYP2C18 → Biochemical Reaction
-
Catalysis
CYP2C9 → Biochemical Reaction
-
Catalysis
CYP2C19 → Biochemical Reaction
-
Catalysis
CYP2C9 → Biochemical Reaction
Edit history (2)
- 2021-07-29 Create
- 2025-07-17 Update Changed PharmGKB to ClinPGx in text