Absorption, Distribution and Excretion
Variable and ranges from 10% to 80%
Menadione and its water soluble derivatives ... are absorbed even in the absence of bile ... /and/ enter the bloodstream directly.
Eighteen hr after intracardiac admin of (3)H-menadione ... to rats fed diet deficient in vit k, 78% of (3)H had been excreted in urine, 3% in feces, and 29% remained in animals. Biliary excretion ... observed in dogs, & 5-10% of (14)c had been excreted by this route 12 hr after oral dose of (14)C-menadione.
Vit k accum in liver, spleen, and lungs. /however/ significant amounts are not stored in body for long periods.
VET: ... Menadione or vit k3 absorbed is converted to k2 for utilization, otherwise it is rapidly eliminated via urine.
The pharmacokinetics of menadione (vitamin K3)... were studied in rabbits after iv injection of 75 mg menadiol sodium diphosphate (Synkayvite). ... Plasma clearance was 0.822 L/min. Systemic clearance in RBCs was 0.407 L/min. Apparent volume of distribution was 30.833 L in plasma and 20.488 L in RBCs. Area under the concn-time curve was 32.453 ug min/ml for plasma and 67.219 ug min/ml for RBCs. /Menadiol sodium diphosphate/

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Metabolism / Metabolites
Hepatic
Distribution studies with menadione tritiated in 6,7-position, ((3)H(6,7))-2-methyl-1,4-naphthaquinone, in rats showed that lipophilic metabolite of menadione, menaquinone-4, 2-methyl-3-geranylgeranyl-1,4-naphthaquinone was present in all tissues examined.
2-methyl-1,4-naphthoquinone yields in rat vit k2(20); yields vit k2(45), and vit k2(50) probably in man. /from table/
...Xenobiotics that are reduced by carbonyl reductases include... menadione... .
Menadione is excreted in part as glucuronide and competes with bilirubin for detoxification mechanism of limited capacity in newborn.
For more Metabolism/Metabolites (Complete) data for MENADIONE (6 total), please visit the HSDB record page.
Hepatic

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Biological Half-Life
The pharmacokinetics of menadione (vitamin K3)... were studied in rabbits after iv injection of 75 mg menadiol sodium diphosphate (Synkayvite). Mean elimination half-life of menadione was 27.17 min in plasma and 35.22 min in red blood cells... . /Menadiol sodium diphosphate/

Toxicity Summary
Menadione (vitamin K3) is involved as a cofactor in the posttranslational gamma-carboxylation of glutamic acid residues of certain proteins in the body. These proteins include the vitamin K-dependent coagulation factors II (prothrombin), VII (proconvertin), IX (Christmas factor), X (Stuart factor), protein C, protein S, protein Zv and a growth-arrest-specific factor (Gas6). In contrast to the other vitamin K-dependent proteins in the blood coagulation cascade, protein C and protein S serve anticoagulant roles. The two vitamin K-dependent proteins found in bone are osteocalcin, also known as bone G1a (gamma-carboxyglutamate) protein or BGP, and the matrix G1a protein or MGP. Gamma-carboxylation is catalyzed by the vitamin K-dependent gamma-carboxylases. The reduced form of vitamin K, vitamin K hydroquinone, is the actual cofactor for the gamma-carboxylases. Proteins containing gamma-carboxyglutamate are called G1a proteins.

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Interactions
Large doses of salicylates... antagonize vitamin k. ... Cmpd with ... antagonist activity is sulfaquinoxaline, a sulfonamide drug used in veterinary medicine... . /vitamin k/
Vitamin k antagonizes inhibitory effect of /acenocoumarol, phenprocoumon, anisindione, diphenadione, and phenindione/ on hepatic synthesis of vitamin k dependent clotting proteins... . /vitamin k/

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Non-Human Toxicity Values
LD50 Mouse oral 500 mg/kg
LD50 Mouse ip 50 mg/kg
LD50 Rat ip 75 mg/kg
LD50 Mouse sc 138 mg/kg

Therapeutic Uses
The synthetic water soluble forms of vitamin K (menadione, menadiol) have long since been considered inferior to vitamin K1 (phytonadione) in the treatment of drug-induced hypoprothrombinemia.
Menadione (vitamin K3) a redox cycling quinone, is a clinically important chemotherapeutic agent. ...
Menadione, or vitamin K3 (VK3), a potent oxidative stress inducer, has been recently used as an effective and remarkably safe cytotoxic drug for treatment of several human tumors. ...

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Drug Warnings
... Probably should not be given to newborn infants or women during last few wk of pregnancy.
Menadione is ineffective for the treatment of warfarin and superwarfarin toxicity. It elicits a poor response and should not be used.
Vitamin K /SRP: phytonadione preferred/ must be administered with great care to patients to whom anticoagulants have been given to combat intravascular clotting. ... The vitamin must be "titrated" against the anticoagulant, lest the patient be re-exposed to the same threat of clotting that led to anticoagulants therapy in the first place. No such problem exists in treating persons poisoned accidentally or suicidally by anticoagulant rodenticides. There is no evidence that vitamin K produces in normal persons any excessive tendency of the blood to clot. /vitamin K/
Menadione...can induce hemolysis in individuals who are genetically deficient in glucose-6-phosphate dehydrogenase.
For more Drug Warnings (Complete) data for MENADIONE (6 total), please visit the HSDB record page.

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Pharmacodynamics
Menadione (Vitamin K3) is a fat-soluble vitamin precursor that is converted into menaquinone in the liver. Vitamin K1 and K2 are the naturally occurring types of vitamin K. The former, which is also known as phylloquinone, is synthesized by plants and can be found in such foods as spinach, broccoli, lettuce, and soybeans. The latter, sometimes alternatively referred to as menaquinone, is primarily produced by bacteria in the anterior part of the gut and the intestines. Vitamin K3, on the other hand, is one of the many manmade versions of vitamin K. Also called menadione, this yellowish, synthetic crystalline substance is converted into the active form of the K2 vitamin inside of the animal body. While a vitamin K deficiency can be dangerous, especially to infants that may easily suffer from extensive hemorrhaging, an overdose can be as equally detrimental. Newborns that are administered too great a dosage of vitamin K3 can suffer from kernicterus, a form of severe brain damage that may produce decreased movement, loss of appetite, seizures, deafness, mental retardation, and even death. This condition is associated with an abnormally high concentration of bilirubin, a bile pigment, in the tissues of the brain, which can be caused by the presence of K3. For this reason, K3 is less often utilized medically than it was in former times.

C11H8O2

172.1800

172.052

58-27-5

4055

Bright yellow crystals
YELLOW NEEDLES FROM ALC, PETROLEUM ETHER

1.225 g/cm3

304.5ºC at 760 mmHg

105-107 °C(lit.)

113.8ºC

2.011

0

2

0

13

289

0

O=C1C(C([H])([H])[H])=C([H])C(C2=C([H])C([H])=C([H])C([H])=C21)=O

MJVAVZPDRWSRRC-UHFFFAOYSA-N

InChI=1S/C11H8O2/c1-7-6-10(12)8-4-2-3-5-9(8)11(7)13/h2-6H,1H3

2-methylnaphthalene-1,4-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~125 mg/mL (~725.98 mM)
Ethanol : ~9.09 mg/mL (~52.79 mM)
H2O : ~0.1 mg/mL (~0.58 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (12.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (12.08 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (12.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)