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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
Structure of PHYTONADIONE, (E)-

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

HIDE SMILES / InChI

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P38435
Gene ID: 2677.0
Gene Symbol: GGCX
Target Organism: Homo sapiens (Human)
Target ID: Q9BQB6
Gene ID: 79001.0
Gene Symbol: VKORC1
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
VITAMIN K1

Approved Use

Vitamin 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 Date

1983
Primary
VITAMIN K1

Approved Use

Vitamin 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 Date

1983
Preventing
VITAMIN K1

Approved Use

Vitamin 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 Date

1983
Secondary
MEPHYTON

Approved Use

MEPHYTON 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 Date

1955
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
32.5 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
146 ng × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
4 h
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

Doses

DosePopulationAdverse 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
n = 1
Health Status: unhealthy
Condition: overdose of brodifacoum
Age Group: 39 years
Sex: M
Population Size: 1
Sources:
1000 mg single, intravenous
MTD
Dose: 1000 mg
Route: intravenous
Route: single
Dose: 1000 mg
Sources:
unhealthy, adult
n = 2
Health Status: unhealthy
Condition: HCC
Age Group: adult
Sex: unknown
Population Size: 2
Sources:
PubMed

PubMed

TitleDatePubMed
Femoral neuropathy and anticoagulants.
1972 Jul
Bleeding from self-administration of phenindione: a detailed case study.
1976 Aug
Virucidal activity of retinal.
1979 Sep
Specificity of increased des-gamma-carboxyprothrombin in hepatocellular carcinoma after vitamin K1 injection.
1987 Aug
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 Aug 19
Anticoagulant-related intracerebral hemorrhage in patients with prosthetic heart valves--report of two cases.
1991 Nov
Skin necrosis, a rare complication of coumarin therapy.
1992
Vitamin B12-associated localized scleroderma and its treatment.
2004 Sep
[Molecular mechanisms of vitamin K action in the bone homeostasis].
2005 May
Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat.
2006 Apr
Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats.
2006 Oct
Sorafenib combined vitamin K induces apoptosis in human pancreatic cancer cell lines through RAF/MEK/ERK and c-Jun NH2-terminal kinase pathways.
2010 Jul
Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme.
2010 Nov 4
Matrix Gla protein metabolism in vascular smooth muscle and role in uremic vascular calcification.
2011 Aug 19
Dietary vitamin K alleviates the reduction in testosterone production induced by lipopolysaccharide administration in rat testis.
2011 Jul
An endogenous vitamin K-dependent mechanism regulates cell proliferation in the brain subventricular stem cell niche.
2012 Apr
Warfarin induces cardiovascular damage in mice.
2013 Nov
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.
2013 Sep 5
Vitamin K1 exerts antiproliferative effects and induces apoptosis in three differently graded human colon cancer cell lines.
2015
Vitamin K1 distribution following intravenous vitamin K1-fat emulsion administration in rats.
2015 Dec
Phylloquinone (Vitamin K1): Occurrence, Biosynthesis and Functions.
2017
Patents

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
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
Created
by admin
on Fri Dec 15 15:50:52 GMT 2023
Edited
by admin
on Fri Dec 15 15:50:52 GMT 2023
Record UNII
S5Z3U87QHF
Record Status Validated (UNII)
Record Version
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Name Type Language
PHYTONADIONE, (E)-
Common Name English
NSC-270681
Code English
SYNTHEX P
Common Name English
PHYTONADIONE [JAN]
Common Name English
PHYLLOQUINONE, (E)-
Common Name English
PHYLLOQUINONE E-FORM [MI]
Common Name English
PHYTOMENADIONE, (E)-
Common Name English
MONODION
Common Name English
2-METHYL-3-((7R,11R,E)-3,7,11,15-TETRAMETHYLHEXADEC-2-EN-1-YL)NAPHTHALENE-1,4-DIONE
Systematic Name English
2-METHYL-3-((2E,7R,11R)-3,7,11,15-TETRAMETHYL-2-HEXADECENYL)-1,4-NAPHTHALENEDIONE
Systematic Name English
Code System Code Type Description
WHO INTERNATIONAL PHARMACOPEIA
PHYTONADIONE, (E)-
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
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.
NSC
270681
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY
PUBCHEM
5284607
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY
FDA UNII
S5Z3U87QHF
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY
MERCK INDEX
m8762
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY Merck Index
HSDB
3162
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY
CAS
84-80-0
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY
ECHA (EC/EINECS)
201-564-2
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY
WIKIPEDIA
Phytomenadione
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY
DRUG BANK
DB01022
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY
EPA CompTox
DTXSID8023472
Created by admin on Fri Dec 15 15:50:52 GMT 2023 , Edited by admin on Fri Dec 15 15:50:52 GMT 2023
PRIMARY