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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, (Z)-

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-ODDKJFTJSA-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
Bleeding from self-administration of phenindione: a detailed case study.
1976 Aug
Anticoagulant-related intracerebral hemorrhage in patients with prosthetic heart valves--report of two cases.
1991 Nov
The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia.
1997 Nov 1
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 Jan
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
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
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 Jan
Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis.
2017
Phylloquinone (Vitamin K1): Occurrence, Biosynthesis and Functions.
2017
Vitamin K plasma levels determination in human health.
2017 May 1
Finding the optimal dose of vitamin K1 to treat vitamin K deficiency and to avoid anaphylactoid reactions.
2017 Oct
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 15:36:57 GMT 2023
Edited
by admin
on Fri Dec 15 15:36:57 GMT 2023
Record UNII
UW760MCX0Y
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PHYTONADIONE, (Z)-
Common Name English
CIS-PHYLLOQUINONE
Common Name English
1,4-NAPHTHALENEDIONE, 2-METHYL-3-(3,7,11,15-TETRAMETHYL-2-HEXADECENYL)-, (R-(R*,R*-(Z)))-
Common Name English
PHYTOMENADIONE, (Z)-
Common Name English
1,4-NAPHTHALENEDIONE, 2-METHYL-3-((2Z,7R,11R)-3,7,11,15-TETRAMETHYL-2-HEXADECENYL)-
Systematic Name English
PHYLLOQUINONE, (Z)-
Common Name English
CIS-VITAMIN K1
Common Name English
1,4-NAPHTHALENEDIONE, 2-METHYL-3-((2Z,7R,11R)-3,7,11,15-TETRAMETHYL-2-HEXADECEN-1-YL)-
Systematic Name English
PHYLLOQUINONE, CIS-
Common Name English
Code System Code Type Description
PUBCHEM
9846607
Created by admin on Fri Dec 15 15:36:57 GMT 2023 , Edited by admin on Fri Dec 15 15:36:57 GMT 2023
PRIMARY
FDA UNII
UW760MCX0Y
Created by admin on Fri Dec 15 15:36:57 GMT 2023 , Edited by admin on Fri Dec 15 15:36:57 GMT 2023
PRIMARY
EPA CompTox
DTXSID70166864
Created by admin on Fri Dec 15 15:36:57 GMT 2023 , Edited by admin on Fri Dec 15 15:36:57 GMT 2023
PRIMARY
CAS
16033-41-3
Created by admin on Fri Dec 15 15:36:57 GMT 2023 , Edited by admin on Fri Dec 15 15:36:57 GMT 2023
PRIMARY