Vitamin K1

Identification

Summary

Vitamin K1 is a fat soluble vitamin used to treat hemorrhagic conditions in infants and coumarin overdoses.

Brand Names
Aquamephyton, Infuvite, Infuvite Pediatric, Mephyton, Mvi Pediatric, Phytonadione
Generic Name
Phylloquinone
Commonly known or available as Vitamin K1
DrugBank Accession Number
DB01022
Background

Vitamin K1, also called phylloquinone or phytonadione, is a fat soluble vitamin.17,18 Phylloquinone is a cofactor of the enzyme γ-carboxylase, which modifies and activates precursors to coagulation factors II, VII, IX, and X.7,8,6 It is indicated in the treatment of coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by deficiency or interference in the activity of vitamin K.17

Phylloquinone has been synthesized since at least 1939,16 and was approved by the FDA prior to 1955.19

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 450.6957
Monoisotopic: 450.349780716
Chemical Formula
C31H46O2
Synonyms
  • 2-Methyl-3-(3,7,11,15-tetramethyl-2-hexadecenyl)-1,4-naphthalenedione
  • 2-Methyl-3-[(2E)-3,7,11,15-tetramethyl-2-hexadecenyl]naphthoquinone
  • 2-Methyl-3-phytyl-1,4-naphthochinon
  • 2-Methyl-3-phytyl-1,4-naphthoquinone
  • 3-Phytylmenadione
  • alpha-Phylloquinone
  • Fitomenadiona
  • Phyllochinon
  • Phyllochinonum
  • Phylloquinone
  • Phythyl-menadion
  • Phytomenadione
  • Phytomenadionum
  • Phytonadione
  • Phytonadionum
  • Phytylmenadione
  • trans-Phylloquinone
  • Vitamin K
  • Vitamin K1
  • α-phylloquinone
External IDs
  • NSC-270681

Pharmacology

Indication

Oral phylloquinone is indicated to treat prothrombin deficiency caused by coumarin or indanedione derivatives; and hypoprothrombinemia secondary to antibacterial therapy, salicylates, or obstructive jaundice or biliary fistulas with concomitant bile salt administration.18

Parenteral (intravenous, intramuscular, and subcutaneous) phylloquinone is indicated to treat coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by vitamin K deficiency or some interference with vitamin K activity.17 These indications include the above indications as well as hypoprothrombinemia secondary to sprue, ulcerative colitis, celiac disease, intestinal resection, pancreatic cystic fibrosis, or regional enteritis; or hypoprothrombinemia caused by interference with vitamin k metabolism.17

Pharmacology
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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Phylloquinone is a vitamin K indicated in the treatment of coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by deficiency or interference in the activity of vitamin K.17 It has a long duration of action as vitamin K is cycled in the body,6 and a wide therapeutic index as large doses can be tolerated.9,18 Patients should have their prothrombin time monitored during therapy and healthcare professionals should be aware of the increased risk of hypersensitivity reactions with parenteral administration.18

Mechanism of action

Vitamin K is a cofactor of gamma-carboxylase.7,8 Gamma carboxylase attaches carboxylic acid functional groups to glutamate, allowing precursors of factors II, VII, IX, and X to bind calcium ions.6 Binding of calcium ions converts these clotting factors to their active form, which are then secreted from hepatocytes into the blood, restoring normal clotting function.18

Vitamin K may also carboxylate matrix proteins in chondrocytes, inhibiting calcification of joints, and may increase type II collagen.10 The role of vitamin K in osteroarthritis,10 bone density,11 and vascular calcification12 is currently under investigation.

TargetActionsOrganism
AVitamin K-dependent gamma-carboxylase
substrate
inducer
cofactor
Humans
UOsteocalcin
agonist
Humans
Absorption

A 4 µg oral dose of phylloquinone is 13% ± 9% bioavailable, with a Tmax of 4.7 ± 0.8 hours.7 1.5 ± 0.8 nmol is found in the plasma compartment, and 3.6 ± 3.4 nmol is found in the second compartment.7

A 10 mg intramuscular phylloquinone dose is 89.2% ± 25.4% bioavailable.14 The same dose reaches a mean Cmax of 67 ± 30 ng/mL, with a mean Tmax of 9.2 ± 6.6 hours, and an AUC of 1700 ± 500 h*ng/mL.14

A 10 mg intravenous phylloquinone dose has a mean AUC of 1950 ± 450 h*ng/mL.14

Volume of distribution

The steady state volume of distribution of phylloquinone is 20 ± 6 L in subjects who are also taking phenprocoumon therapy.15

Protein binding

Not Available

Metabolism

Phylloquinone's phytyl side chain is omega hydroxylated by CYP4F2.5 The side chain is then cleaved to 5 or 7 carbons long, and then glucuronidated prior to elimination.1,2,3,4

Vitamin Ks in general undergo a cycle of reduction to vitamin K hydroquinone by vitamin K epoxide reductase (VKOR), oxidation to vitamin K epoxide by gamma-glutamyl carboxylase, and converted back to vitamin K by VKOR.6

Hover over products below to view reaction partners

Route of elimination

Intravenous phylloquinone is 36% eliminated in the feces in 5 days and 22% recovered in urine in 3 days.1,13

Half-life

Intravenous phylloquinone has an initial half life of 22 minutes, followed by a half life of 125 minutes.1

Clearance

Intravenous phylloquinone is 90% cleared in 2 hours, and 99% cleared in 8 hours.1,13 A 10 mg intravenous dose of phylloquinone has a mean clearance of 91 ± 24 mL/min.14

Adverse Effects
Adverseeffects
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Toxicity

High doses of vitamin K1 are not associated with toxicity.6 Intravenous administration has been associated with an increased risk of toxicity.9 These patients should be treated with symptomatic and supportive measures.

The intravenous LD50 in mice is 1170 mg/kg and the oral LD50 is >24180 mg/kg.18

Pathways
PathwayCategory
Enoxaparin Action PathwayDrug action
Fondaparinux Action PathwayDrug action
Lepirudin Action PathwayDrug action
Alteplase Action PathwayDrug action
Anistreplase Action PathwayDrug action
Urokinase Action PathwayDrug action
Phenindione Action PathwayDrug action
Warfarin Action PathwayDrug action
Acenocoumarol Action PathwayDrug action
Dicumarol Action PathwayDrug action
Argatroban Action PathwayDrug action
Ximelagatran Action PathwayDrug action
Tenecteplase Action PathwayDrug action
Aminocaproic Acid Action PathwayDrug action
Dicoumarol Action PathwayDrug action
Phenprocoumon Action PathwayDrug action
Heparin Action PathwayDrug action
Ardeparin Action PathwayDrug action
Bivalirudin Action PathwayDrug action
Streptokinase Action PathwayDrug action
Reteplase Action PathwayDrug action
Tranexamic Acid Action PathwayDrug action
Aprotinin Action PathwayDrug action
Vitamin K MetabolismMetabolic
CoagulationPhysiological
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirPhylloquinone may decrease the excretion rate of Abacavir which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Phylloquinone which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Phylloquinone which could result in a higher serum level.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be decreased when used in combination with Phylloquinone.
AcetaminophenAcetaminophen may decrease the excretion rate of Phylloquinone which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Phylloquinone which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Phylloquinone which could result in a higher serum level.
AclidiniumPhylloquinone may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastinePhylloquinone may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Phylloquinone which could result in a higher serum level.
Interactions
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Food Interactions
No interactions found.

Products

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Product Images
International/Other Brands
Aqua-Mephyton / Konakion
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AquaMEPHYTONInjection, emulsion10 mg/1mLIntramuscular; Intravenous; SubcutaneousTeligent Pharma, Inc.2018-03-07Not applicableUS flag
AquaMEPHYTONInjection, emulsion2 mg/1mLIntramuscular; Intravenous; SubcutaneousTeligent Pharma, Inc.2018-03-07Not applicableUS flag
MephytonTablet5 mg/1OralAvera McKennan Hospital2015-03-092017-05-24US flag69189 170420180907 15195 1h1s1ee
MephytonTablet5 mg/1OralRebel Distributors1955-09-30Not applicableUS flag
MephytonTablet5 mg/1OralPd Rx Pharmaceuticals, Inc.1955-09-302017-03-20US flag
MephytonTablet5 mg/1OralKAISER FOUNDATION HOSPITALS2013-07-292019-02-28US flag00187 1704 05 nlmimage10 e045f00f
MephytonTablet5 mg/1OralPhysicians Total Care, Inc.2006-03-21Not applicableUS flag
MephytonTablet5 mg/1OralA-S Medication Solutions2013-03-19Not applicableUS flag50090 175320180913 8702 lz6o12
MephytonTablet5 mg/1OralCarilion Materials Management2013-03-19Not applicableUS flag68151 015820180913 8702 gj5t3l
MephytonTablet5 mg/1OralMerck Sharp & Dohme Limited1955-09-302008-10-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PhytonadioneTablet5 mg/1OralMajor Pharmaceuticals2018-05-15Not applicableUS flag
PhytonadioneTablet5 mg/1OralOceanside Pharmaceuticals2018-04-23Not applicableUS flag
PhytonadioneInjection, emulsion1 mg/0.5mLParenteralAmphastar Pharmaceuticals, Inc.1988-03-242009-12-16US flag
PhytonadioneInjection, emulsion1 mg/0.5mLParenteralCardinal Health2003-04-182013-09-30US flag
PhytonadioneTablet5 mg/1OralAmneal Pharmaceuticals NY LLC2018-05-15Not applicableUS flag
PhytonadioneInjection, emulsion1 mg/0.5mLParenteralGeneral Injectables & Vaccines2012-09-14Not applicableUS flag
PhytonadioneTablet5 mg/1OralCadila Healthcare Limited2019-02-22Not applicableUS flag
PhytonadioneTablet5 mg/1OralAmerican Health Packaging2018-06-21Not applicableUS flag
PhytonadioneTablet5 mg/1OralNorthstar Rx Llc.2019-10-18Not applicableUS flag
PhytonadioneInjection, emulsion1 mg/0.5mLIntramuscular; Parenteral; SubcutaneousGeneral Injectables & Vaccines2010-04-012013-07-01US flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
KONAKION MM INJECTION 10 mg/mlInjection10 mg/mlIntravenousROCHE SINGAPORE PTE. LTD.1996-01-27Not applicable
KONAKION MM PAEDIATRIC INJECTION 2 mg/0.2 mlInjection2 mg/0.2mlIntramuscular; IntravenousROCHE SINGAPORE PTE. LTD.1997-07-23Not applicable
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Adeks - DpsPhylloquinone (0.1 mg / mL) + Ascorbic acid (45 mg / mL) + Beta carotene (1 mg / mL) + Biotin (15 mcg / mL) + Cyanocobalamin (4 mcg / mL) + Nicotinamide (6 mg / mL) + Panthenol (3 mg / mL) + Pyridoxine hydrochloride (0.6 mg / mL) + Riboflavin (0.6 mg / mL) + Thiamine (0.5 mg / mL) + Vitamin A palmitate (1500 unit / mL) + Vitamin D (400 unit / mL) + Vitamin E (40 unit / mL) + Zinc (5 mg / mL)Solution / dropsOralAxcan Pharma1995-12-312007-10-01Canada flag
Adeks TabletsPhylloquinone (0.15 mg) + Ascorbic acid (60 mg) + Beta carotene (3 mg) + Biotin (50 mcg) + Cholecalciferol (400 unit) + Cyanocobalamin (12 mcg) + Folic acid (0.2 mg) + Niacin (10 mg) + Calcium pantothenate (10 mg) + Pyridoxine (1.5 mg) + Riboflavin (1.3 mg) + Thiamine (1.2 mg) + Vitamin A palmitate (4000 unit) + Vitamin E (150 unit) + Zinc (7.5 mg)TabletOralAxcan Pharma1998-01-202011-04-20Canada flag
Adult Infuvite Multiple VitaminsPhylloquinone (150 ug/10mL) + Ascorbic acid (200 mg/10mL) + Biotin (60 ug/10mL) + Cholecalciferol (200 [iU]/10mL) + Cyanocobalamin (5 ug/10mL) + Dexpanthenol (15 mg/10mL) + Riboflavin 5'-phosphate sodium (3.6 mg/10mL) + Folic acid (600 ug/10mL) + Nicotinamide (40 mg/10mL) + Pyridoxine hydrochloride (6 mg/10mL) + Thiamine hydrochloride (6 mg/10mL) + Vitamin A palmitate (3300 [iU]/10mL) + alpha-Tocopherol acetate (10 [iU]/10mL)Injection, solutionIntravenousSandoz Manufacturing Inc2003-06-16Not applicableUS flag
Adult Infuvite Multiple VitaminsPhylloquinone (150 ug/10mL) + Ascorbic acid (200 mg/10mL) + Biotin (60 ug/10mL) + Cholecalciferol (200 [iU]/10mL) + Cyanocobalamin (5 ug/10mL) + Dexpanthenol (15 mg/10mL) + Riboflavin 5'-phosphate sodium (3.6 mg/10mL) + Folic acid (600 ug/10mL) + Nicotinamide (40 mg/10mL) + Pyridoxine hydrochloride (6 mg/10mL) + Thiamine hydrochloride (6 mg/10mL) + Vitamin A palmitate (3300 [iU]/10mL) + alpha-Tocopherol acetate (10 [iU]/10mL)Injection, solutionIntravenousSandoz Manufacturing Inc2003-06-16Not applicableUS flag
Adult Infuvite Multiple VitaminsPhylloquinone (150 ug/10mL) + Ascorbic acid (200 mg/10mL) + Biotin (60 ug/10mL) + Cholecalciferol (200 [iU]/10mL) + Cyanocobalamin (5 ug/10mL) + Dexpanthenol (15 mg/10mL) + Riboflavin 5'-phosphate sodium (3.6 mg/10mL) + Folic acid (600 ug/10mL) + Nicotinamide (40 mg/10mL) + Pyridoxine hydrochloride (6 mg/10mL) + Thiamine hydrochloride (6 mg/10mL) + Vitamin A palmitate (3300 [iU]/10mL) + alpha-Tocopherol acetate (10 [iU]/10mL)Injection, solutionIntravenousSandoz Manufacturing Inc2005-05-18Not applicableUS flag
Adult Infuvite Multiple VitaminsPhylloquinone (150 ug/10mL) + Ascorbic acid (200 mg/10mL) + Biotin (60 ug/10mL) + Cholecalciferol (200 [iU]/10mL) + Cyanocobalamin (5 ug/10mL) + Dexpanthenol (15 mg/10mL) + Riboflavin 5'-phosphate sodium (3.6 mg/10mL) + Folic acid (600 ug/10mL) + Nicotinamide (40 mg/10mL) + Pyridoxine hydrochloride (6 mg/10mL) + Thiamine hydrochloride (6 mg/10mL) + Vitamin A palmitate (3300 [iU]/10mL) + alpha-Tocopherol acetate (10 [iU]/10mL)Injection, solutionIntravenousSandoz Manufacturing Inc2005-05-18Not applicableUS flag
CALCIDOSE 1200 MG/800 IU/65 MCG EFERVESAN TABLET, 45 ADETPhylloquinone (65 mcg) + Calcium (1200 mg) + Cholecalciferol (800 iu)Tablet, effervescentOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
CALCIDOSE 600 MG/400 IU/32.5 MCG EFERVESAN TABLET, 30 ADETPhylloquinone (32.5 mcg) + Calcium (600 mg) + Cholecalciferol (400 iu)Tablet, effervescentOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
CALCIDOSE 600 MG/400 IU/32.5 MCG EFERVESAN TABLET, 60 ADETPhylloquinone (32.5 mcg) + Calcium (600 mg) + Cholecalciferol (400 iu)Tablet, effervescentOralNEUTEC İLAÇ SAN. TİC. A.Ş.2020-08-14Not applicableTurkey flag
Infuvite Adult Multiple VitaminsPhylloquinone (150 ug/10mL) + Ascorbic acid (200 mg/10mL) + Biotin (60 ug/10mL) + Cholecalciferol (200 [iU]/10mL) + Cyanocobalamin (5 ug/10mL) + Dexpanthenol (15 mg/10mL) + Riboflavin 5'-phosphate sodium (3.6 mg/10mL) + Folic acid (600 ug/10mL) + Nicotinamide (40 mg/10mL) + Pyridoxine hydrochloride (6 mg/10mL) + Thiamine hydrochloride (6 mg/10mL) + Vitamin A palmitate (3300 [iU]/10mL) + alpha-Tocopherol acetate (10 [iU]/10mL)Injection, solutionIntravenousSandoz Manufacturing Inc2003-06-16Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
PhytonadionePhylloquinone (10 mg/1mL)Injection, emulsionParenteralSquare Pharmaceuticals Ltd.2018-04-10Not applicableUS flag
PhytonadionePhylloquinone (1 mg/0.5mL)Injection, emulsionParenteralSquare Pharmaceuticals Ltd.2018-04-10Not applicableUS flag
VITALIPID N-ADULT 10 AMPULPhylloquinone (15 mcg/mL) + Ergocalciferol (0.5 mcg/mL) + Vitamin A palmitate (99 mcg/mL) + Vitamin E (0.91 mg/mL)Injection, emulsionIntravenousFRESENİUS KABİ İLAÇ SAN. VE TİC. LTD. ŞTİ.2020-08-14Not applicableTurkey flag

Categories

ATC Codes
B02BA01 — Phytomenadione
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as vitamin k compounds. These are quinone lipids containing a methylated naphthoquinone ring structure, and vary in the aliphatic side chain attached at the 3-position.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Quinone and hydroquinone lipids
Direct Parent
Vitamin K compounds
Alternative Parents
Diterpenoids / Naphthoquinones / Quinones / Aryl ketones / Organic oxides / Hydrocarbon derivatives
Substituents
Aromatic homopolycyclic compound / Aryl ketone / Benzenoid / Diterpenoid / Hydrocarbon derivative / Ketone / Naphthalene / Naphthoquinone / Organic oxide / Organic oxygen compound
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
phylloquinones (CHEBI:18067) / Vitamin K (LMPR02030028)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
S5Z3U87QHF
CAS number
84-80-0
InChI Key
MBWXNTAXLNYFJB-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

References

Synthesis Reference

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

US5744624
General References
  1. Barkhan P, Shearer MJ: Metabolism of vitamin K1 (phylloquinone) in man. Proc R Soc Med. 1977 Feb;70(2):93-6. [Article]
  2. McBurney A, Shearer MJ, Barkhan P: Preparative isolation and characterization of the urinary aglycones of vitamin K1 (phylloquinone in man. Biochem Med. 1980 Dec;24(3):250-67. doi: 10.1016/0006-2944(80)90020-4. [Article]
  3. Shearer MJ, Fu X, Booth SL: Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr. 2012 Mar 1;3(2):182-95. doi: 10.3945/an.111.001800. [Article]
  4. Turck D, Bresson JL, Burlingame B, Dean T, Fairweather-Tait S, Heinonen M, Hirsch-Ernst KI, Mangelsdorf I, McArdle HJ, Naska A, Nowicka G, Pentieva K, Sanz Y, Siani A, Sjodin A, Stern M, Tome D, Van Loveren H, Vinceti M, Willatts P, Lamberg-Allardt C, Przyrembel H, Tetens I, Dumas C, Fabiani L, Ioannidou S, Neuhauser-Berthold M: Dietary reference values for vitamin K. EFSA J. 2017 May 22;15(5):e04780. doi: 10.2903/j.efsa.2017.4780. eCollection 2017 May. [Article]
  5. Edson KZ, Prasad B, Unadkat JD, Suhara Y, Okano T, Guengerich FP, Rettie AE: Cytochrome P450-dependent catabolism of vitamin K: omega-hydroxylation catalyzed by human CYP4F2 and CYP4F11. Biochemistry. 2013 Nov 19;52(46):8276-85. doi: 10.1021/bi401208m. Epub 2013 Nov 7. [Article]
  6. Imbrescia K, Moszczynski Z: Vitamin K . [Article]
  7. Jones KS, Bluck LJ, Wang LY, Coward WA: A stable isotope method for the simultaneous measurement of vitamin K1 (phylloquinone) kinetics and absorption. Eur J Clin Nutr. 2008 Nov;62(11):1273-81. doi: 10.1038/sj.ejcn.1602859. Epub 2007 Aug 1. [Article]
  8. Shearer MJ, Newman P: Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res. 2014 Mar;55(3):345-62. doi: 10.1194/jlr.R045559. Epub 2014 Jan 31. [Article]
  9. Ingold CJ, Sergent SR: Phytonadione (Vitamin K1) . [Article]
  10. Chin KY: The Relationship between Vitamin K and Osteoarthritis: A Review of Current Evidence. Nutrients. 2020 Apr 25;12(5). pii: nu12051208. doi: 10.3390/nu12051208. [Article]
  11. Weber P: Vitamin K and bone health. Nutrition. 2001 Oct;17(10):880-7. doi: 10.1016/s0899-9007(01)00709-2. [Article]
  12. Shioi A, Morioka T, Shoji T, Emoto M: The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification. Nutrients. 2020 Feb 23;12(2). pii: nu12020583. doi: 10.3390/nu12020583. [Article]
  13. Shearer MJ, Mallinson CN, Webster GR, Barkhan P: Clearance from plasma and excretion in urine, faeces and bile of an intravenous dose of tritiated vitamin K 1 in man. Br J Haematol. 1972 May;22(5):579-88. doi: 10.1111/j.1365-2141.1972.tb05704.x. [Article]
  14. Soedirman JR, De Bruijn EA, Maes RA, Hanck A, Gruter J: Pharmacokinetics and tolerance of intravenous and intramuscular phylloquinone (vitamin K1) mixed micelles formulation. Br J Clin Pharmacol. 1996 Jun;41(6):517-23. doi: 10.1046/j.1365-2125.1996.03847.x. [Article]
  15. Øie S, Trenk D, Guentert TW, Mosberg H, Jähnchen E: Disposition of vitamin K1 after intravenous and oral administration to subjects on phenprocoumon therapy International Journal of Pharmaceutics. 1988 Jun 15;48(1-3):223-230. [Article]
  16. Fieser LF: Synthesis of Vitamin K1 J Am Chem Soc. 1939 Dec 1;61(12):3467-3475. [Article]
  17. FDA Review: Vitamin K1 Subcutaneous, Intramuscular, and Intravenous Injection [Link]
  18. Dailymed: Phytonadione Oral Tablet [Link]
  19. FDA Approved Drug Products: Mephyton (Phylloquinone) Oral Tablet [Link]
Human Metabolome Database
HMDB0015157
KEGG Drug
D00148
KEGG Compound
C02059
PubChem Compound
5284607
PubChem Substance
46504528
ChemSpider
4447652
BindingDB
24782
RxNav
8308
ChEBI
18067
ChEMBL
CHEMBL1550
ZINC
ZINC000003831332
Therapeutic Targets Database
DNC001500
PharmGKB
PA450961
PDBe Ligand
PQN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Phytomenadione
PDB Entries
1c51 / 1jb0 / 1qzv / 2o01 / 2pps / 2wsc / 2wse / 2wsf / 3lw5 / 3pcq
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MSDS
Download (72 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedOtherAcute Coronary Syndrome (ACS)1
4CompletedPreventionAtrial Fibrillation1
4CompletedPreventionKidney Diseases1
4CompletedSupportive CareAtrial Fibrillation1
4CompletedTreatmentAcute Pulmonary Embolism (PE)1
4CompletedTreatmentAtrial Fibrillation1
4CompletedTreatmentCalcifications, Vascular1
4CompletedTreatmentCervical Artery Dissection1
4CompletedTreatmentDeep Vein Thrombosis / Pulmonary Embolism1
4CompletedTreatmentDiabetes / Impaired Glucose Tolerance1

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
  • Hoffmann la roche inc
  • Aton pharma inc
  • Glaxosmithkline
  • International medication system
  • Hospira inc
Packagers
  • Amphastar Pharmaceuticals
  • Apotheca Inc.
  • Aton Pharma Inc.
  • Baxter International Inc.
  • Bimeda Inc.
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Draxis Specialty Pharmaceuticals Inc.
  • Gallipot
  • General Injectables and Vaccines Inc.
  • GRB SRL
  • H.J. Harkins Co. Inc.
  • Hospira Inc.
  • Kaiser Foundation Hospital
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Professional Co.
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandoz
  • Southwood Pharmaceuticals
  • Spectrum Pharmaceuticals
Dosage Forms
FormRouteStrength
Solution / dropsOral
Injection, emulsionIntramuscular; Intravenous; Subcutaneous10 mg/1mL
Injection, emulsionIntramuscular; Intravenous; Subcutaneous2 mg/1mL
Tablet, effervescentOral
Tablet, effervescentOral2500 mg
Powder, for solutionIntravenous
SolutionIntramuscular1 mg
SolutionIntramuscular10 mg
InjectionIntramuscular; Intravenous; Subcutaneous1 mg
InjectionIntramuscular; Intravenous10 mg
TabletOral
Syrup100 mg/5ml
InjectionIntravenous
SolutionIntravenous; Oral10 MG/ML
SolutionOral10 MG/ML
SolutionOral2 MG/0.2ML
Solution / dropsOral20 MG/ML
Tablet, coated10 MG
SolutionIntravenous; Oral10 mg
SolutionIntravenous; Oral
SolutionIntramuscular; Intravenous; Oral
InjectionIntravenous10 mg/ml
InjectionIntramuscular; Intravenous2 mg/0.2ml
SolutionIntramuscular; Intravenous; Oral10 mg
Injection, powder, lyophilized, for solutionIntravenous
TabletOral5 mg/1
LiquidIntravenous
Tablet, chewableOral
KitOral
Powder
InjectionIntravenous
Injection, solutionIntravenous
Tablet, sugar coatedOral
Tablet, film coatedOral
Injection, emulsionIntramuscular; Intravenous; Subcutaneous1 mg/0.5mL
Injection, emulsionIntramuscular; Parenteral; Subcutaneous1 mg/0.5mL
Injection, emulsionParenteral1 mg/0.5mL
Injection, emulsionParenteral10 mg/1mL
LiquidIntramuscular2 mg / mL
Capsule, coatedOral
Injection
CapsuleOral
Injection, powder, for solutionParenteral
Injection, solution
TabletOral
SolutionIntravenous
InjectionIntravenous330 iu/ml
Injection, solution, concentrateIntravenous
InjectionIntravenous230 iu/ml
Injection, emulsionIntravenous
EmulsionIntravenous
InjectionIntramuscular; Intravenous; Subcutaneous
SolutionIntramuscular; Intravenous; Subcutaneous10 mg / mL
EmulsionIntramuscular; Intravenous; Subcutaneous10 mg / mL
EmulsionIntramuscular; Intravenous; Subcutaneous2 mg / mL
SolutionIntramuscular; Intravenous; Subcutaneous2 mg / mL
Solution10 mg/1ml
InjectionIntramuscular10 mg/2ml
InjectionIntramuscular50 mg/2ml
Injection, solution10 MG/2ML
InjectionParenteral10 mg
SolutionParenteral10 mg
EmulsionIntramuscular; Intravenous; Subcutaneous10 mg
SolutionIntramuscular; Intravenous; Subcutaneous1 mg
InjectionIntramuscular; Intravenous; Subcutaneous10 mg
TabletOral100 mcg
Capsule
Solution2 mg/1ml
Injection, suspension10 mg/1ml
Injection, solution10 mg/1ml
Prices
Unit descriptionCostUnit
Phytonadione crystal111.13USD g
Phytonadione liquid66.0USD g
Vitamin k1 liquid35.0USD g
Mephyton 5 mg tablet5.95USD tablet
Vitamin K1 Pediatric 2 mg/ml4.79USD ml
Vitamin K1 10 mg/ml2.76USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)-20 °CPhysProp
boiling point (°C)142.5 °C at 1.00E-03 mm HgPhysProp
water solubilityInsoluble in waterFDA Review: Vitamine K1
Predicted Properties
PropertyValueSource
Water Solubility5.92e-05 mg/mLALOGPS
logP8.48ALOGPS
logP9.7ChemAxon
logS-6.9ALOGPS
pKa (Strongest Basic)-7.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity142.96 m3·mol-1ChemAxon
Polarizability55.92 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8941
Caco-2 permeable+0.7993
P-glycoprotein substrateSubstrate0.6643
P-glycoprotein inhibitor IInhibitor0.8581
P-glycoprotein inhibitor IIInhibitor0.9503
Renal organic cation transporterNon-inhibitor0.7232
CYP450 2C9 substrateNon-substrate0.7852
CYP450 2D6 substrateNon-substrate0.827
CYP450 3A4 substrateSubstrate0.6854
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7542
Ames testNon AMES toxic0.8945
CarcinogenicityNon-carcinogens0.9183
BiodegradationNot ready biodegradable0.9051
Rat acute toxicity1.1603 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5675
hERG inhibition (predictor II)Inhibitor0.5
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MSGC-MSsplash10-002r-2930000000-2b32596edebbe7e02cf7
GC-MS Spectrum - GC-MS (1 TMS)GC-MSsplash10-0002-1290000000-fa752c2db990f115c3c6
GC-MS Spectrum - GC-MS (2 TMS)GC-MSsplash10-0002-8269080000-4bdc9b3a41d7d08b7265
GC-MS Spectrum - GC-MS (2 TMS)GC-MSsplash10-0002-7379080000-ba90762b738ee84b3151
GC-MS Spectrum - GC-MS (2 TMS)GC-MSsplash10-014i-6749020000-c4e58ef0e538e224dad4
GC-MS Spectrum - GC-MS (2 TMS)GC-MSsplash10-0g4i-3149020000-ad93d4a26002eefa74ce
GC-MS Spectrum - GC-MS (2 TMS)GC-MSsplash10-00xr-5397040000-221a2f93d46494325e33
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0udl-9740400000-e47d11ed7b15a667d611
GC-MS Spectrum - EI-BGC-MSsplash10-0udi-2540900000-d08585615fbc2418786a
GC-MS Spectrum - GC-MSGC-MSsplash10-002r-2930000000-2b32596edebbe7e02cf7
GC-MS Spectrum - GC-MSGC-MSsplash10-0002-1290000000-fa752c2db990f115c3c6
GC-MS Spectrum - GC-MSGC-MSsplash10-0002-8269080000-4bdc9b3a41d7d08b7265
GC-MS Spectrum - GC-MSGC-MSsplash10-0002-7379080000-ba90762b738ee84b3151
GC-MS Spectrum - GC-MSGC-MSsplash10-014i-6749020000-c4e58ef0e538e224dad4
GC-MS Spectrum - GC-MSGC-MSsplash10-0g4i-3149020000-ad93d4a26002eefa74ce
GC-MS Spectrum - GC-MSGC-MSsplash10-00xr-5397040000-221a2f93d46494325e33
GC-MS Spectrum - GC-MSGC-MSsplash10-002r-2930000000-2b32596edebbe7e02cf7
GC-MS Spectrum - GC-MSGC-MSsplash10-0002-1290000000-fa752c2db990f115c3c6
GC-MS Spectrum - GC-MSGC-MSsplash10-0002-8269080000-4bdc9b3a41d7d08b7265
GC-MS Spectrum - GC-MSGC-MSsplash10-0002-7379080000-ba90762b738ee84b3151
GC-MS Spectrum - GC-MSGC-MSsplash10-014i-6749020000-c4e58ef0e538e224dad4
GC-MS Spectrum - GC-MSGC-MSsplash10-0g4i-3149020000-ad93d4a26002eefa74ce
GC-MS Spectrum - GC-MSGC-MSsplash10-00xr-5397040000-221a2f93d46494325e33
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
Inducer
Cofactor
General Function
Gamma-glutamyl carboxylase activity
Specific Function
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vit...
Gene Name
GGCX
Uniprot ID
P38435
Uniprot Name
Vitamin K-dependent gamma-carboxylase
Molecular Weight
87560.065 Da
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Olson RE: The function and metabolism of vitamin K. Annu Rev Nutr. 1984;4:281-337. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. Shearer MJ, Newman P: Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res. 2014 Mar;55(3):345-62. doi: 10.1194/jlr.R045559. Epub 2014 Jan 31. [Article]
  8. Imbrescia K, Moszczynski Z: Vitamin K . [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Structural molecule activity
Specific Function
Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium.
Gene Name
BGLAP
Uniprot ID
P02818
Uniprot Name
Osteocalcin
Molecular Weight
10962.445 Da
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. [Article]
  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. [Article]
  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. [Article]
  4. Askim M: [Vitamin K in the Norwegian diet and osteoporosis]. Tidsskr Nor Laegeforen. 2001 Sep 20;121(22):2614-6. [Article]
  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. [Article]
  6. Hauschka PV, Reid ML: Vitamin K dependence of a calcium-binding protein containing gamma-carboxyglutamic acid in chicken bone. J Biol Chem. 1978 Dec 25;253(24):9063-8. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Not Available
Specific Function
Not Available
Gene Name
CYP4F2
Uniprot ID
P78329
Uniprot Name
Phylloquinone omega-hydroxylase CYP4F2
Molecular Weight
59852.825 Da
References
  1. Edson KZ, Prasad B, Unadkat JD, Suhara Y, Okano T, Guengerich FP, Rettie AE: Cytochrome P450-dependent catabolism of vitamin K: omega-hydroxylation catalyzed by human CYP4F2 and CYP4F11. Biochemistry. 2013 Nov 19;52(46):8276-85. doi: 10.1021/bi401208m. Epub 2013 Nov 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Prenyltransferase that mediates the formation of menaquinone-4 (MK-4) and coenzyme Q10. MK-4 is a vitamin K2 isoform present at high concentrations in the brain, kidney and pancreas, and is required for endothelial cell development. Mediates the conversion of phylloquinone (PK) into MK-4, probably by cleaving the side chain of phylloquinone (PK) to release 2-methyl-1,4-naphthoquinone (menadione; K3) and then prenylating it with geranylgeranyl pyrophosphate (GGPP) to form MK-4. Also plays a role in cardiovascular development independently of MK-4 biosynthesis, by acting as a coenzyme Q10 biosynthetic enzyme: coenzyme Q10, also named ubiquinone, plays an important antioxidant role in the cardiovascular system. Mediates biosynthesis of coenzyme Q10 in the Golgi membrane, leading to protect cardiovascular tissues from NOS3/eNOS-dependent oxidative stress.
Specific Function
Antioxidant activity
Gene Name
UBIAD1
Uniprot ID
Q9Y5Z9
Uniprot Name
UbiA prenyltransferase domain-containing protein 1
Molecular Weight
36830.745 Da
References
  1. Shearer MJ, Newman P: Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res. 2014 Mar;55(3):345-62. doi: 10.1194/jlr.R045559. Epub 2014 Jan 31. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Product of
General Function
Vitamin-k-epoxide reductase (warfarin-sensitive) activity
Specific Function
Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the...
Gene Name
VKORC1
Uniprot ID
Q9BQB6
Uniprot Name
Vitamin K epoxide reductase complex subunit 1
Molecular Weight
18234.3 Da
References
  1. Shearer MJ, Newman P: Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res. 2014 Mar;55(3):345-62. doi: 10.1194/jlr.R045559. Epub 2014 Jan 31. [Article]
  2. Begent LA, Hill AP, Steventon GB, Hutt AJ, Pallister CJ, Cowell DC: Characterization and purification of the vitamin K1 2,3 epoxide reductases system from rat liver. J Pharm Pharmacol. 2001 Apr;53(4):481-6. doi: 10.1211/0022357011775776. [Article]

Drug created on June 13, 2005 13:24 / Updated on October 16, 2021 12:31