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Identification
NamePhylloquinone
Accession NumberDB01022  (APRD00464)
Typesmall molecule
Groupsapproved
Description

Phylloquinone is often called vitamin K1. 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.

Structure
Thumb
Synonyms
SynonymLanguageCode
2-Methyl-3-phytyl-1,4-naphthoquinoneNot AvailableNot Available
3-PhytylmenadioneNot AvailableNot Available
alpha-PhylloquinoneNot AvailableNot Available
PhyllochinonNot AvailableNot Available
PhylloquinoneNot AvailableNot Available
Phythyl-menadionGermanNot Available
PhytomenadioneNot AvailableNot Available
PhytonadioneNot AvailableNot Available
PhytylmenadioneNot AvailableNot Available
trans-PhylloquinoneNot AvailableNot Available
Vitamin K1Not AvailableNot Available
α-phylloquinoneNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Aqua-MephytonNot Available
KonakionNot Available
MephytonNot Available
Brand mixturesNot Available
Categories
CAS number84-80-0
WeightAverage: 450.6957
Monoisotopic: 450.349780716
Chemical FormulaC31H46O2
InChI KeyMBWXNTAXLNYFJB-NKFFZRIASA-N
InChI
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
IUPAC Name
2-methyl-3-[(2E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]-1,4-dihydronaphthalene-1,4-dione
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassPrenol Lipids
SubclassQuinone and Hydroquinone Lipids
Direct parentVitamin K Compounds
Alternative parentsDiterpenes; Naphthoquinones; p-Benzoquinones; p-Quinones; Benzene and Substituted Derivatives; Polyamines
Substituentsnaphthoquinone; naphthalene; p-benzoquinone; p-quinone; quinone; benzene; ketone; polyamine; carbonyl group
Classification descriptionThis compound belongs to the vitamin k compounds. These are compounds quinone lipids containing a methylated naphthoquinone ring structure, and vary in the aliphatic side chain attached at the 3-position.
Pharmacology
IndicationFor the treatment of haemorrhagic conditions in infants, antidote for coumarin anticoagulants in hypoprothrombinaemia.
PharmacodynamicsPhylloquinone is a vitamin, indicated in the treatment of 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. Phylloquinone aqueous colloidal solution of vitamin K1 for parenteral injection, possesses 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).
Mechanism of actionVitamin 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.
AbsorptionOral phylloquinone is adequately absorbed from the gastrointestinal tract only if bile salts are present. After absorption, phylloquinone is initially concentrated in the liver, but the concentration declines rapidly. Very little vitamin K accumulates in tissues.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationAlmost no free unmetabolized vitamin K appears in bile or urine.
Half lifeNot Available
ClearanceNot Available
ToxicityThe intravenous LD50 of phylloquinone in the mouse is 41.5 and 52 mL/kg for the 0.2% and 1% concentrations, respectively.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Vitamin K MetabolismMetabolicSMP00464
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.8941
Caco-2 permeable + 0.7993
P-glycoprotein substrate Substrate 0.6643
P-glycoprotein inhibitor I Inhibitor 0.8581
P-glycoprotein inhibitor II Inhibitor 0.9503
Renal organic cation transporter Non-inhibitor 0.7232
CYP450 2C9 substrate Non-substrate 0.7852
CYP450 2D6 substrate Non-substrate 0.827
CYP450 3A4 substrate Substrate 0.6854
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Inhibitor 0.8949
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7542
Ames test Non AMES toxic 0.8945
Carcinogenicity Non-carcinogens 0.9183
Biodegradation Not ready biodegradable 0.9051
Rat acute toxicity 1.1603 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.5675
hERG inhibition (predictor II) Inhibitor 0.5
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
  • Hoffmann la roche inc
  • Aton pharma inc
  • Glaxosmithkline
  • International medication system
  • Hospira inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionIntramuscular
Injection, solutionIntravenous
Injection, solutionSubcutaneous
Prices
Unit descriptionCostUnit
Phytonadione crystal111.13USDg
Phytonadione liquid66.0USDg
Vitamin k1 liquid35.0USDg
Mephyton 5 mg tablet5.95USDtablet
Vitamin K1 Pediatric 2 mg/ml4.79USDml
Vitamin K1 10 mg/ml2.76USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point-20 °CPhysProp
boiling point142.5 °C at 1.00E-03 mm HgPhysProp
water solubilityInsoluble in waterNot Available
logP9.3Not Available
Predicted Properties
PropertyValueSource
water solubility5.92e-05 g/lALOGPS
logP8.48ALOGPS
logP9.7ChemAxon
logS-6.9ALOGPS
pKa (strongest basic)-7.2ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area34.14ChemAxon
rotatable bond count14ChemAxon
refractivity142.96ChemAxon
polarizability55.92ChemAxon
number of rings2ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraGC-MS
References
Synthesis Reference

Manfred Dorner, “Method of making vitamin K1.” U.S. Patent US5744624, issued June, 1964.

US5744624
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00148
KEGG CompoundC02059
ChEBI18067
ChEMBLCHEMBL1550
Therapeutic Targets DatabaseDNC001500
PharmGKBPA450961
Drug Product Database243876
RxListhttp://www.rxlist.com/cgi/generic3/phytonadione.htm
Drugs.comhttp://www.drugs.com/cdi/phytonadione.html
WikipediaPhytonadione
ATC CodesB02BA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(72 KB)
Interactions
Drug Interactions
Drug
WarfarinPhytonadione (vitamin K) may antagonize the anticoagulant effects of warfarin. Monitor for changes in prothrombin time if phytonadione intake (either via supplements or vitamin K-rich foods) is increased or decreased.
Food InteractionsNot Available

Targets

1. Vitamin K-dependent gamma-carboxylase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Vitamin K-dependent gamma-carboxylase P38435 Details

References:

  1. Morris DP, Soute BA, Vermeer C, Stafford DW: Characterization of the purified vitamin K-dependent gamma-glutamyl carboxylase. J Biol Chem. 1993 Apr 25;268(12):8735-42. Pubmed
  2. Tuan RS: Vitamin K-dependent gamma-glutamyl carboxylase activity in the chick embryonic chorioallantoic membrane. J Biol Chem. 1979 Feb 25;254(4):1356-64. Pubmed
  3. Reedstrom CK, Suttie JW: Comparative distribution, metabolism, and utilization of phylloquinone and menaquinone-9 in rat liver. Proc Soc Exp Biol Med. 1995 Sep;209(4):403-9. Pubmed
  4. Tasatargil A, Cadir B, Dalaklioglu S, Yurdakonar E, Caglar S, Turkay C: Effects of vitamin K1 supplementation on vascular responsiveness and oxidative stress in a rat femoral osteotomy model. Cell Biochem Funct. 2007 Sep-Oct;25(5):485-90. Pubmed
  5. Olson RE: The function and metabolism of vitamin K. Annu Rev Nutr. 1984;4:281-337. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Osteocalcin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Osteocalcin P02818 Details

References:

  1. Sato Y, Tsuru T, Oizumi K, Kaji M: Vitamin K deficiency and osteopenia in disuse-affected limbs of vitamin D-deficient elderly stroke patients. Am J Phys Med Rehabil. 1999 Jul-Aug;78(4):317-22. Pubmed
  2. Schurgers LJ, Dissel PE, Spronk HM, Soute BA, Dhore CR, Cleutjens JP, Vermeer C: Role of vitamin K and vitamin K-dependent proteins in vascular calcification. Z Kardiol. 2001;90 Suppl 3:57-63. Pubmed
  3. Vermeer C, Wolf J, Craciun AM, Knapen MH: Bone markers during a 6-month space flight: effects of vitamin K supplementation. J Gravit Physiol. 1998 Oct;5(2):65-9. Pubmed
  4. Askim M: [Vitamin K in the Norwegian diet and osteoporosis] Tidsskr Nor Laegeforen. 2001 Sep 20;121(22):2614-6. Pubmed
  5. Kawana K, Takahashi M, Hoshino H, Kushida K: Circulating levels of vitamin K1, menaquinone-4, and menaquinone-7 in healthy elderly Japanese women and patients with vertebral fractures and patients with hip fractures. Endocr Res. 2001 Aug;27(3):337-43. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on January 20, 2014 21:55