Konakion MM Mechanism of Action

Pharmacology: Properties and effects: Vitamin K₁ (phytomenadione), the active ingredient of Phytomenadione (Konakion), is a procoagulant factor. As a component of a hepatic carboxylase system, vitamin K₁ is involved in the post-translational carboxylation of clotting factors II (prothrombin), VII, IX and X and the clotting inhibitors protein C and protein S. Coumarins inhibit the reduction of vitamin K₁ (quinone form) to vitamin K₁ hydroquinone and also prevent the vitamin K₁ epoxide arising after carboxylation from being reduced to the quinone form.
Vitamin K₁ is an antagonist of coumarin-type anticoagulants, e.g. phenprocoumon (active ingredient of Marcoumar). It does not, however, neutralize the activity of heparin (active ingredient of Liquemin); protamine is the antagonist of heparin. Vitamin K₁ is ineffective in hereditary hypoprothrombinemia or hypoprothrombinemia induced by severe hepatic failure. In the MM ampoules, vitamin K₁ is solubilized by means of a physiological colloid system of bile acid-lecithin micelles, a transport medium also found in the body.
Pharmacokinetics: Absorption: A pharmacokinetic study indicated that the MM solution of vitamin K₁ given orally is rapidly and effectively absorbed.
Oral doses of vitamin K₁ are absorbed primarily from the middle portions of the small intestine. Systemic availability following oral dosing is approximately 50%, with a wide range of interindividual variability. Onset of action occurs approximately 1-3 hours after intravenous administration and 4-6 hours after oral doses.
Distribution: The primary distribution compartment corresponds to the plasma volume. In blood plasma 90% of vitamin K₁ is bound to lipoproteins (VLDL fraction). Normal plasma concentrations of vitamin K₁ range from 0.4 to 1.2 ng/mL. After i.v. administration of 10 mg vitamin K₁ Phytomenadione (Konakion) MM, the plasma level after 1 hour is about 500 ng/mL and about 50 ng/mL at 12 hours. Vitamin K₁ does not readily cross the placenta and is poorly distributed into breast milk.
Metabolism: Vitamin K₁ is rapidly converted into more polar metabolites, including vitamin K₁-2,3-epoxide. Some of this metabolite is reconverted into vitamin K₁.
Elimination: Following metabolic degradation, vitamin K₁ is excreted in the bile and urine as glucuronide and sulfate conjugates. The terminal half-life in adults is 14 ± 6 h after i.v. administration and 10 ± 6 h after oral administration. Less than 10% of a dose is excreted unchanged in the urine.
Pharmacokinetics in special clinical situations: Intestinal absorption of vitamin K₁ is impaired by various conditions, including malabsorption syndromes, short bowel syndrome, biliary atresia and pancreatic insufficiency. The dosage for this patient group should therefore be at the lower end of the recommended range (see section Dosage & Administration).