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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:29
Primary Accession Number DB01022
Secondary Accession Number
  • APRD00464
Name Phytonadione
Drug Type
  • Approved
  • Small Molecule
Description Phytonadione 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.
Synonyms
  1. 2', 3'-trans-Vitamin K1
  2. 2-Methyl-3-phythyl-1,4-naphthochinon
  3. 3-Phytylmenadione
  4. Antihemorrhagic vitamin
  5. Phyllochinon
  6. Phylloquinone
  7. Phythyl-menadion (GERMAN)
  8. Phytomenadione
  9. Phytylmenadione
  10. Vitamin K
  11. Vitamin K1
  12. alpha-Phylloquinone
Brand Names
  1. Aqua-Mephytin
  2. AquaMEPHYTON
  3. Combinal K1
  4. K-Ject
  5. Kativ N
  6. Kephton
  7. Kinadion
  8. Konakion
  9. Mephyton
  10. Mono-Kay
  11. Monodion
  12. Synthex P
Brand Mixtures Not Available
Chemical IUPAC Name 2-methyl-3-(3,7,11,15-tetramethylhexadec-2-enyl)naphthalene-1,4-dione
Chemical Formula C31H46O2
Chemical Structure Structure
CAS Registry Number 84-80-0
InChI Identifier InChI=1/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
InChI Key MBWXNTAXLNYFJB-UHFFFAOYAF
KEGG Drug D00148 Link Image
KEGG Compound C02059 Link Image
PubChem Compound 4812 Link Image
PubChem Substance 5148 Link Image
ChEBI ID 18067 Link Image
PharmGKB ID PA450961 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00243876 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/phytonadione.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Phytonadione Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 450.6957
Monoisotopic Molecular Weight 450.3498
State Liquid
Melting Point -20 oC
Experimental Water Solubility Insoluble in water Source: PhysProp
Predicted Water Solubility 5.92e-05 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 9.3 Source: PhysProp
Predicted LogP 8.48 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -6.88 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CC1=C(C)C(=O)C2=CC=CC=C2C1=O
Canonical SMILES CC(C)CCCC(C)CCCC(C)CCCC(C)=CCC1=C(C)C(=O)C2=CC=CC=C2C1=O
Drug Category
  • Antifibrinolytic Agents
  • Vitamins
  • Vitamins (Vitamin K)
ATC Codes Not Available
AHFS Codes Not Available
Indication For the treatment of haemorrhagic conditions in infants, antidote for coumarin anticoagulants in hypoprothrombinaemia
Pharmacology Phytonadione 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. Phytonadione 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 Action 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, VII, IX and X. Gamma-carboxylation converts these inactive precursors into active coagulation factors which are secreted by hepatocytes into the blood. Supplementing with Phytonadione results in a relief of vitamin K deficiency symptoms which include easy bruisability, epistaxis, gastrointestinal bleeding, menorrhagia and hematuria.
Absorption 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.
Toxicity The intravenous LD50 of phytonadione in the mouse is 41.5 and 52 mL/kg for the 0.2% and 1% concentrations, respectively.
Protein Binding Not Available
Biotransformation Not Available
Half Life Not Available
Dosage Forms
Form Route
Injection, solution Intramuscular
Injection, solution Intravenous
Injection, solution Subcutaneous
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Vitamin K-dependent gamma-carboxylase
  2. Osteocalcin
Drug Target 1 [top]
Target 1 ID 448
Target 1 Name Vitamin K-dependent gamma-carboxylase
Target 1 Synonyms
  1. EC 6.4.-.-
  2. Gamma-glutamyl carboxylase
  3. Vitamin K gamma glutamyl carboxylase
Target 1 Gene Name GGCX
Target 1 Protein Sequence >Vitamin K-dependent gamma-carboxylase 
MAVSAGSARTSPSSDKVQKDKAELISGPRQDSRIGKLLGFEWTDLSSWRRLVTLLNRPTD
PASLAVFRFLFGFLMVLDIPQERGLSSLDRKYLDGLDVCRFPLLDALRPLPLDWMYLVYT
IMFLGALGMMLGLCYRISCVLFLLPYWYVFLLDKTSWNNHSYLYGLLAFQLTFMDANHYW
SVDGLLNAHRRNAHVPLWNYAVLRGQIFIVYFIAGVKKLDADWVEGYSMEYLSRHWLFSP
FKLLLSEELTSLLVVHWGGLLLDLSAGFLLFFDVSRSIGLFFVSYFHCMNSQLFSIGMFS
YVMLASSPLFCSPEWPRKLVSYCPRRLQQLLPLKAAPQPSVSCVYKRSRGKSGQKPGLRH
QLGAAFTLLYLLEQLFLPYSHFLTQGYNNWTNGLYGYSWDMMVHSRSHQHVKITYRDGRT
GELGYLNPGVFTQSRRWKDHADMLKQYATCLSRLLPKYNVTEPQIYFDIWVSINDRFQQR
IFDPRVDIVQAAWSPFQRTSWVQPLLMDLSPWRAKLQEIKSSLDNHTEVVFIADFPGLHL
ENFVSEDLGNTSIQLLQGEVTVELVAEQKNQTLREGEKMQLPAGEYHKVYTTSPSPSCYM
YVYVNTTELALEQDLAYLQELKEKVENGSETGPLPPELQPLLEGEVKGGPEPTPLVQTFL
RRQQRLQEIERRRNTPFHERFFRFLLRKLYVFRRSFLMTCISLRNLILGRPSLEQLAQEV
TYANLRPFEAVGELNPSNTDSSHSNPPESNPDPVHSEF
Target 1 Number of Residues 770
Target 1 Molecular Weight 87562
Target 1 Theoretical pI 8.10
Target 1 GO Classification
Function
catalytic activity
lyase activity
carbon-carbon lyase activity
carboxy-lyase activity
gamma-glutamyl carboxylase activity
Process
physiological process
metabolism
macromolecule metabolism
biopolymer metabolism
biopolymer modification
protein modification
peptidyl-amino acid modification
peptidyl-glutamic acid modification
peptidyl-glutamic acid carboxylation
Component
Not Available
Target 1 General Function Involved in gamma-glutamyl carboxylase activity
Target 1 Specific Function Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium binding gamma-carboxyglutamate (Gla) residues with the concomitant convertion of the reduced hydroquinone form of vitamin K to vitamin K epoxide
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 61-81
  • 114-134
  • 137-157
  • 293-313
  • 362-382
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 184028 Link Image
Target 1 UniProtKB/Swiss-Prot ID P38435 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name VKGC_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Endoplasmic reticulum
  • endoplasmic reticulum membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >2277 bp 
ATGGCGGTGTCTGCCGGGTCCGCGCGGACCTCGCCCAGCTCAGATAAAGTACAGAAAGAC
AAGGCTGAACTGATCTCAGGGCCCAGGCAGGACAGCCGAATAGGGAAACTCTTGGGTTTT
GAGTGGACAGATTTGTCCAGTTGGCGGAGGCTGGTGACCCTGCTGAATCGACCAACGGAC
CCTGCAAGCTTAGCTGTCTTTCGTTTTCTTTTTGGGTTCTTGATGGTGCTAGACATTCCC
CAGGAGCGGGGGCTCAGCTCTCTGGACCGGAAATACCTTGATGGGCTGGATGTGTGCCGC
TTCCCCTTGCTGGATGCCCTACGCCCACTGCCACTTGACTGGATGTATCTTGTCTACACC
ATCATGTTTCTGGGGGCACTGGGCATGATGCTGGGCCTGTGCTACCGGATAAGCTGTGTG
TTATTCCTGCTGCCATACTGGTATGTGTTTCTCCTGGACAAGACATCATGGAACAACCAC
TCCTATCTGTATGGGTTGTTGGCCTTTCAGCTAACATTCATGGATGCAAACCACTACTGG
TCTGTGGACGGTCTGCTGAATGCCCATAGGAGGAATGCCCACGTGCCCCTTTGGAACTAT
GCAGTGCTCCGTGGCCAGATCTTCATTGTGTACTTCATTGCGGGTGTGAAAAAGCTGGAT
GCAGACTGGGTTGAAGGCTATTCCATGGAATATTTGTCCCGGCACTGGCTCTTCAGTCCC
TTCAAACTGCTGTTGTCTGAGGAGCTGACTAGCCTGCTGGTCGTGCACTGGGGTGGGCTG
CTGCTTGACCTCTCAGCTGGTTTCCTGCTCTTTTTTGATGTCTCAAGATCCATTGGCCTG
TTCTTTGTGTCCTACTTCCACTGCATGAATTCCCAGCTTTTCAGCATTGGTATGTTCTCC
TACGTCATGCTGGCCAGCAGCCCTCTCTTCTGCTCCCCTGAGTGGCCTCGGAAGCTGGTG
TCCTACTGCCCCCAAAGGTTGCAACAACTGTTGCCCCTCAAGGCAGCCCCTCAGCCCAGT
GTTTCCTGTGTGTATAAGAGGAGCCGGGGCAAAAGTGGCCAGAAGCCAGGGCTGCGCCAT
CAGCTGGGAGCTGCCTTCACCCTGCTCTACCTCCTGGAGCAGCTATTCCTGCCCTATTCT
CATTTTCTCACCCAGGGCTATAACAACTGGACAAATGGGCTGTATGGCTATTCCTGGGAC
ATGATGGTGCACTCCCGTTCCCACCAGCACGTGAAGATCACCTACCGTGATGGCCGCACT
GGCGAACTGGGCTACCTTAACCCTGGGGTATTTACACAGAGTCGGCGATGGAAGGATCAT
GCAGACATGCTGAAGCAATATGCCACTTGCCTGAGCCGCCTGCTTCCCAAGTATAATGTC
ACTGAGCCCCAGATCTACTTTGATATTTGGGTCTCCATCAATGACCGCTTCCAGCAGAGG
ATTTTTGACCCTCGTGTGGACATCGTGCAGGCCGCTTGGTCACCCTTTCAGCGCACATCC
TGGGTGCAACCACTCTTGATGGACCTGTCTCCCTGGAGGGCCAAGTTACAGGAAATCAAG
AGCAGCCTAGACAACCACACTGAGGTGGTCTTCATTGCAGATTTCCCTGGACTGCACTTG
GAGAATTTTGTGAGTGAAGACCTGGGCAACACTAGCATCCAGCTGCTGCAGGGGGAAGTG
ACTGTGGAGCTTGTGGCAGAACAGAAGAACCAGACTCTTCGAGAGGGAGAAAAAATGCAG
TTGCCTGCTGGTGAGTACCATAAGGTGTATACGACATCACCTAGCCCTTCTTGCTACATG
TACGTCTATGTCAACACTACAGAGCTTGCACTGGAGCAAGACCTGGCATATCTGCAAGAA
TTAAAGGAAAAGGTGGAGAATGGAAGTGAAACAGGGCCTCTACCCCCAGAGCTGCAGCCT
CTGTTGGAAGGGGAAGTAAAAGGGGGCCCTGAGCCAACACCTCTGGTTCAGACCTTTCTT
AGACGCCAACAAAGGCTCCAGGAGATTGAACGCCGGCGAAATACTCCTTTCCATGAGCGA
TTCTTCCGCTTCTTGTTGCGAAAGCTCTATGTCTTTCGCCGCAGCTTCCTGATGACTTGT
ATCTCACTTCGAAATCTGATATTAGGCCGTCCTTCCCTGGAGCAGCTGGCCCAGGAGGTG
ACTTATGCAAACTTGAGACCCTTTGAGGCAGTTGGAGAACTGAATCCCTCAAACACGGAT
TCTTCACATTCTAATCCTCCTGAGTCAAATCCTGATCCTGTCCACTCAGAGTTCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID GGCX Link Image
Target 1 GenAtlas ID GGCX Link Image
Target 1 HGNC ID HGNC:4247 Link Image
Target 1 Chromosome Location 2
Target 1 Locus 2p12
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Spronk HM, Farah RA, Buchanan GR, Vermeer C, Soute BA: Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors. Blood. 2000 Nov 15;96(10):3650-2. [PubMed Link Image]
  2. Wu SM, Cheung WF, Frazier D, Stafford DW: Cloning and expression of the cDNA for human gamma-glutamyl carboxylase. Science. 1991 Dec 13;254(5038):1634-6. [PubMed Link Image]
  3. Wu SM, Stafford DW, Frazier LD, Fu YY, High KA, Chu K, Sanchez-Vega B, Solera J: Genomic sequence and transcription start site for the human gamma-glutamyl carboxylase. Blood. 1997 Jun 1;89(11):4058-62. [PubMed Link Image]
  4. Brenner B, Sanchez-Vega B, Wu SM, Lanir N, Stafford DW, Solera J: A missense mutation in gamma-glutamyl carboxylase gene causes combined deficiency of all vitamin K-dependent blood coagulation factors. Blood. 1998 Dec 15;92(12):4554-9. [PubMed Link Image]
Target 1 Drug References
  1. 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 Link Image]
  2. 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 Link Image]
  3. Olson RE: The function and metabolism of vitamin K. Annu Rev Nutr. 1984;4:281-337. [PubMed Link Image]
  4. 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 Link Image]
  5. 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 Link Image]
Drug Target 2 [top]
Target 2 ID 798
Target 2 Name Osteocalcin
Target 2 Synonyms
  1. BGP
  2. Bone Gla-protein
  3. Gamma-carboxyglutamic acid-containing protein
  4. Osteocalcin precursor
Target 2 Gene Name BGLAP
Target 2 Protein Sequence >Osteocalcin precursor 
MRALTLLALLALAALCIAGQAGAKPSGAESSKGAAFVSKQEGSEVVKRPRRYLYQWLGAP
VPYPDPLEPRREVCELNPDCDELADHIGFQEAYRRFYGPV
Target 2 Number of Residues 101
Target 2 Molecular Weight 10963
Target 2 Theoretical pI 7.18
Target 2 GO Classification
Function
binding
ion binding
cation binding
calcium ion binding
Process
regulation of biological process
regulation of physiological process
regulation of organismal physiological process
regulation of bone remodeling
regulation of ossification
regulation of bone mineralization
Component
extracellular region
Target 2 General Function Involved in calcium ion binding
Target 2 Specific Function Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-23
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 36093 Link Image
Target 2 UniProtKB/Swiss-Prot ID P02818 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name OSTC_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Secreted protein
Target 2 Gene Sequence >303 bp 
ATGAGAGCCCTCACACTCCTCGCCCTATTGGCCCTGGCCGCACTTTGCATCGCTGGCCAG
GCAGGTGCGAAGCCCAGCGGTGCAGAGTCCAGCAAAGGTGCAGCCTTTGTGTCCAAGCAG
GAGGGCAGCGAGGTAGTGAAGAGACCCAGGCGCTACCTGTATCAATGGCTGGGAGCCCCA
GTCCCCTACCCGGATCCCCTGGAGCCCAGGAGGGAGGTGTGTGAGCTCAATCCGGACTGT
GACGAGTTGGCTGACCACATCGGCTTTCAGGAGGCCTATCGGCGCTTCTACGGCCCGGTC
TAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID BGLAP Link Image
Target 2 GenAtlas ID BGLAP Link Image
Target 2 HGNC ID HGNC:1043 Link Image
Target 2 Chromosome Location 1
Target 2 Locus 1q25-q31
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Kiefer MC, Saphire AC, Bauer DM, Barr PJ: The cDNA and derived amino acid sequences of human and bovine bone Gla protein. Nucleic Acids Res. 1990 Apr 11;18(7):1909. [PubMed Link Image]
  2. Celeste AJ, Rosen V, Buecker JL, Kriz R, Wang EA, Wozney JM: Isolation of the human gene for bone gla protein utilizing mouse and rat cDNA clones. EMBO J. 1986 Aug;5(8):1885-90. [PubMed Link Image]
  3. Poser JW, Esch FS, Ling NC, Price PA: Isolation and sequence of the vitamin K-dependent protein from human bone. Undercarboxylation of the first glutamic acid residue. J Biol Chem. 1980 Sep 25;255(18):8685-91. [PubMed Link Image]
Target 2 Drug 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 Link Image]
  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 Link Image]
  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 Link Image]
  4. Askim M: [Vitamin K in the Norwegian diet and osteoporosis] Tidsskr Nor Laegeforen. 2001 Sep 20;121(22):2614-6. [PubMed Link Image]
  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 Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.