Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C31H46O2 |
| Molecular Weight | 450.6957 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CC1=C(C)C(=O)C2=C(C=CC=C2)C1=O
InChI
InChIKey=MBWXNTAXLNYFJB-NKFFZRIASA-N
InChI=1S/C31H46O2/c1-22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,18-20,22-24H,9-17,21H2,1-6H3/b25-20+/t23-,24-/m1/s1
| Molecular Formula | C31H46O2 |
| Molecular Weight | 450.6957 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 1 |
| Optical Activity | UNSPECIFIED |
Phylloquinone is often called vitamin K1 or phytonadione. It is a fat-soluble vitamin that is stable to air and moisture but decomposes in sunlight. It is found naturally in a wide variety of green plants. Phylloquinone is also an antidote for coumatetralyl. Vitamin K is needed for the posttranslational modification of certain proteins, mostly required for blood coagulation. MEPHYTON (Phytonadione tablets) are indicated in the following coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity: anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives; hypoprothrombinemia secondary to antibacterial therapy; hypoprothrombinemia secondary to administration of salicylates; hypoprothrombinemia secondary to obstructive jaundice or biliary fistulas but only if bile salts are administered concurrently, since otherwise the oral vitamin K will not be absorbed. MEPHYTON tablets possess the same type and degree of activity as does naturally-occurring vitamin K, which is necessary for the production via the liver of active prothrombin (factor II), proconvertin (factor VII), plasma thromboplastin component (factor IX), and Stuart factor (factor X). The prothrombin test is sensitive to the levels of three of these four factors II, VII, and X. Vitamin K is an essential cofactor for the gamma-carboxylase enzymes, which catalyze the posttranslational gamma-carboxylation of glutamic acid residues in inactive hepatic precursors of coagulation factors II (prothrombin), VII, IX, and X. Gamma-carboxylation converts these inactive precursors into active coagulation factors, which are secreted by hepatocytes into the blood. Supplementing with Phylloquinone results in a relief of vitamin K deficiency symptoms, which include easy bruisability, epistaxis, gastrointestinal bleeding, menorrhagia and hematuria. Oral phytonadione is adequately absorbed from the gastrointestinal tract only if bile salts are present. After absorption, phytonadione is initially concentrated in the liver, but the concentration declines rapidly. Very little vitamin K accumulates in tissues. Little is known about the metabolic fate of vitamin K. Almost no free unmetabolized vitamin K appears in bile or urine. In normal animals and humans, phytonadione is virtually devoid of pharmacodynamic activity. However, in animals and humans deficient in vitamin K, the pharmacological action of vitamin K is related to its normal physiological function; that is, to promote the hepatic biosynthesis of vitamin K-dependent clotting factors. MEPHYTON tablets generally exert their effect within 6 to 10 hours.
CNS Activity
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P38435 Gene ID: 2677.0 Gene Symbol: GGCX Target Organism: Homo sapiens (Human) |
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Target ID: Q9BQB6 Gene ID: 79001.0 Gene Symbol: VKORC1 Target Organism: Homo sapiens (Human) |
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Target ID: CHEMBL2012 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16929463 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Preventing | VITAMIN K1 Approved UseVitamin K1 Injection is indicated in: (1) anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives; (2) prophylaxis and therapy of hemorrhagic disease of the newborn; (3) hypoprothrombinemia due to antibacterial therapy; (3) hypoprothrombinemia secondary to factors limiting absorption or synthesis of vitamin K, e.g., obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, and regional enteritis; (4) other drug-induced hypoprothrombinemia where it is definitely shown that the result is due to interference with vitamin K metabolism, e.g., salicylates. Launch Date1983 |
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| Primary | VITAMIN K1 Approved UseVitamin K1 Injection is indicated in: (1) anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives; (2) prophylaxis and therapy of hemorrhagic disease of the newborn; (3) hypoprothrombinemia due to antibacterial therapy; (3) hypoprothrombinemia secondary to factors limiting absorption or synthesis of vitamin K, e.g., obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, and regional enteritis; (4) other drug-induced hypoprothrombinemia where it is definitely shown that the result is due to interference with vitamin K metabolism, e.g., salicylates. Launch Date1983 |
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| Preventing | VITAMIN K1 Approved UseVitamin K1 Injection is indicated in: (1) anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives; (2) prophylaxis and therapy of hemorrhagic disease of the newborn; (3) hypoprothrombinemia due to antibacterial therapy; (3) hypoprothrombinemia secondary to factors limiting absorption or synthesis of vitamin K, e.g., obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, and regional enteritis; (4) other drug-induced hypoprothrombinemia where it is definitely shown that the result is due to interference with vitamin K metabolism, e.g., salicylates. Launch Date1983 |
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| Secondary | MEPHYTON Approved UseMEPHYTON is indicated in the following coagulation disorders which are due to faulty formation of factors II, VII, IX and X when caused by vitamin K deficiency or interference with vitamin K activity. MEPHYTON tablets are indicated in: anticoagulant-induced prothrombin deficiency caused by coumarin or indanedione derivatives; hypoprothrombinemia secondary to antibacterial therapy; hypoprothrombinemia secondary to administration of salicylates; hypoprothrombinemia secondary to obstructive jaundice or biliary fistulas but only if bile salts are
administered concurrently, since otherwise the oral vitamin K will not be absorbed. Launch Date1955 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
32.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28107923/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHYTONADIONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
146 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28107923/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHYTONADIONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28107923/ |
5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHYTONADIONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
200 mg 1 times / day steady, intravenous Highest studied dose Dose: 200 mg, 1 times / day Route: intravenous Route: steady Dose: 200 mg, 1 times / day Sources: |
unhealthy, 39 years |
|
1000 mg single, intravenous MTD Dose: 1000 mg Route: intravenous Route: single Dose: 1000 mg Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Finding the optimal dose of vitamin K1 to treat vitamin K deficiency and to avoid anaphylactoid reactions. | 2017-10 |
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| Vitamin K plasma levels determination in human health. | 2017-05-01 |
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| Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis. | 2017 |
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| Phylloquinone (Vitamin K1): Occurrence, Biosynthesis and Functions. | 2017 |
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| Vitamin K1 distribution following intravenous vitamin K1-fat emulsion administration in rats. | 2015-12 |
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| Vitamin K1 alleviates streptozotocin-induced type 1 diabetes by mitigating free radical stress, as well as inhibiting NF-κB activation and iNOS expression in rat pancreas. | 2015-01 |
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| Vitamin K1 exerts antiproliferative effects and induces apoptosis in three differently graded human colon cancer cell lines. | 2015 |
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| Vitamin K1 in oral solution or tablets: a crossover trial and two randomized controlled trials to compare effects. | 2014-12 |
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| Warfarin induces cardiovascular damage in mice. | 2013-11 |
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| FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1. | 2013-09-05 |
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| Effects of CYP4F2 polymorphism on response to warfarin during induction phase: a prospective, open-label, observational cohort study. | 2012-04 |
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| An endogenous vitamin K-dependent mechanism regulates cell proliferation in the brain subventricular stem cell niche. | 2012-04 |
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| Matrix Gla protein metabolism in vascular smooth muscle and role in uremic vascular calcification. | 2011-08-19 |
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| Dietary vitamin K alleviates the reduction in testosterone production induced by lipopolysaccharide administration in rat testis. | 2011-07 |
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| Eicosapentaenoic acid reduces warfarin-induced arterial calcification in rats. | 2011-03 |
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| Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. | 2010-11-04 |
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| Sorafenib combined vitamin K induces apoptosis in human pancreatic cancer cell lines through RAF/MEK/ERK and c-Jun NH2-terminal kinase pathways. | 2010-07 |
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| Effects of CYP4F2 genetic polymorphisms and haplotypes on clinical outcomes in patients initiated on warfarin therapy. | 2009-10 |
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| CYP4F2 is a vitamin K1 oxidase: An explanation for altered warfarin dose in carriers of the V433M variant. | 2009-06 |
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| Effect of cell differentiation for neuroblastoma by vitamin k analogs. | 2009-04 |
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| Chronic angiotensin-converting enzyme inhibition up-regulates mouse kidney growth arrest specific-6 protein and the AXL subfamily of receptor tyrosine kinases. | 2008-12 |
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| Gradual improvement of liver function after administration of ursodeoxycholic acid in an infant with a novel ABCB11 gene mutation with phenotypic continuum between BRIC2 and PFIC2. | 2007-11 |
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| Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats. | 2006-10 |
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| APOE genotype makes a small contribution to warfarin dose requirements. | 2006-08 |
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| Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat. | 2006-04 |
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| Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities. | 2006-01 |
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| Timing of fresh frozen plasma administration and rapid correction of coagulopathy in warfarin-related intracerebral hemorrhage. | 2006-01 |
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| Warfarin dose related to apolipoprotein E (APOE) genotype. | 2005-07 |
|
| [Molecular mechanisms of vitamin K action in the bone homeostasis]. | 2005-05 |
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| [Haemostasis. A search for an ideal antithrombotics agent]. | 2005-01-05 |
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| Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage. | 2005 |
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| Vitamin B12-associated localized scleroderma and its treatment. | 2004-09 |
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| A new model of isolated systolic hypertension induced by chronic warfarin and vitamin K1 treatment. | 2003-02 |
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| Pharmacological prevention and regression of arterial remodeling in a rat model of isolated systolic hypertension. | 2002-08 |
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| Matrix gamma-carboxyglutamic acid protein is a key regulator of PTH-mediated inhibition of mineralization in MC3T3-E1 osteoblast-like cells. | 2001-10 |
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| Hepatic failure and encephalopathy attributed to an interaction between acetaminophen and rifampicin. | 2001-04 |
|
| A conserved motif within the vitamin K-dependent carboxylase gene is widely distributed across animal phyla. | 2000-11-17 |
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| The anticoagulant factor, protein S, is produced by cultured human vascular smooth muscle cells and its expression is up-regulated by thrombin. | 2000-03-15 |
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| Chemiluminescence analysis of menadione sodium bisulfite and analgin in pharmaceutical preparations and biological fluids. | 1999-12 |
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| Interaction between fenofibrate and warfarin. | 1998-07-29 |
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| The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia. | 1997-11-01 |
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| Pseudoscleroderma secondary to phytomenadione (vitamin K1) injections: Texier's disease. | 1996-02 |
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| Skin necrosis, a rare complication of coumarin therapy. | 1992 |
|
| Anticoagulant-related intracerebral hemorrhage in patients with prosthetic heart valves--report of two cases. | 1991-11 |
|
| Simultaneous determination of vitamin K1, vitamin K1 2,3-epoxide and menaquinone-4 in human plasma by high-performance liquid chromatography with fluorimetric detection. | 1988-08-19 |
|
| Specificity of increased des-gamma-carboxyprothrombin in hepatocellular carcinoma after vitamin K1 injection. | 1987-08 |
|
| Hematomyelia during anticoagulant therapy. | 1985-11 |
|
| Virucidal activity of retinal. | 1979-09 |
|
| Femoral neuropathy and anticoagulants. | 1972-07 |
|
| Absorption of tritiated vitamin K1 in patients with fat malabsorption. | 1970-12 |
Sample Use Guides
Prophylaxis of Hemorrhagic Disease of the Newborn: A single intramuscular dose of (E)-phytonadione (Vitamin K1 Injection) 0.5 to 1 mg within one hour of birth is recommended. Treatment of Hemorrhagic Disease of the Newborn: 1 mg should be given either subcutaneously or intramuscularly. Anticoagulant-Induced Prothrombin Deficiency in Adults: the dose of 2.5 mg to 10 mg or up to 25 mg is recommended. Hypoprothrombinemia due to other causes: a dosage of 2.5 to 25 mg or more (rarely up to 50 mg) is recommended.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3684371
Curator's Comment: Vitamin K1 (VK1) inhibited the expression of heat-shock protein 72 (Hsp72) but did not affect the constitutive expression of Hsc70 or calnexin in vitro and in vivo. VK1 and VK2 sensitized A549 cells to heat-shock induced cell death, while the compounds alone had no effect on cell viability. The suppression of Hsp72 was apparently at the protein level because the mRNA expression of Hsp72 was unchanged.
Human lymphocytes were incubated with (E)-phytonadione at a dose of 1 uM. At this concentration (E)-phytonadione significantly increased Sister Chromatid Exchange.
| Substance Class |
Chemical
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| Record UNII |
S5Z3U87QHF
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Validated (UNII)
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PHYTONADIONE, (E)-
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PRIMARY | Description: A clear, yellow to amber-coloured, very viscous liquid; odourless or almost odourless. Miscibility: Practically immiscible with water; sparingly miscible with ethanol (~750 g/l) TS; freely miscible with chloroform R and ether R. Category: Anticoagulant.Storage: Phytomenadione should be kept in a tightly closed container, protected from light. Definition: Phytomenadione contains not less than 97.0% and not more than 102.0% of C31H46O2. | ||
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