Acenocoumarol

Absorption	Rapidly absorbed orally with greater than 60% bioavailability. Peak plasma levels are attained 1 to 3 hours following oral administration.
Volume of distribution	The volume of distribution at steady-state appeared to be significantly dose dependent: 78 ml/kg for doses < or = 20 microg/kg and 88 ml/kg for doses > 20 microg/kg respectively
Protein binding	98.7% protein bound, mainly to albumin
Metabolism	Extensively metabolized in the liver via oxidation forming two hydroxy metabolites and keto reduction producing two alcohol metabolites. Reduction of the nitro group produces an amino metabolite which is further transformed to an acetoamido metabolite. Metabolites do not appear to be pharmacologically active. Enzyme Metabolite Reaction Km Vmax Cytochrome P450 1A2 6-Hydroxy-R-acenocoumarol 6-hydroxylation Cytochrome P450 2C9 6-Hydroxy-R-acenocoumarol 6-hydroxylation Cytochrome P450 2C9 7-Hydroxy-R-acenocoumarol 7-hydroxylation Cytochrome P450 2C9 8-Hydroxy-R-acenocoumarol 8-hydroxylation Cytochrome P450 2C19 6-Hydroxy-R-acenocoumarol 6-hydroxylation Cytochrome P450 2C19 7-Hydroxy-R-acenocoumarol 7-hydroxylation Cytochrome P450 2C19 8-Hydroxy-R-acenocoumarol 8-hydroxylation
Route of elimination	Mostly via the kidney as metabolites
Half life	8 to 11 hours.
Clearance	Not Available
Toxicity	The onset and severity of the symptoms are dependent on the individual's sensitivity to oral anticoagulants, the severity of the overdosage, and the duration of treatment. Bleeding is the major sign of toxicity with oral anticoagulant drugs. The most frequent symptoms observed are: cutaneous bleeding (80%), haematuria (with renal colic) (52%), haematomas, gastrointestinal bleeding, haematemesis, uterine bleeding, epistaxis, gingival bleeding and bleeding into the joints. Further symptoms include tachycardia, hypotension, peripheral circulatory disorders due to loss of blood, nausea, vomiting, diarrhoea and abdominal pains.
Affected organisms	Humans and other mammals
Pathways	Pathway Name Acenocoumarol Pathway