Absorption, Distribution and Excretion
Absorption rates vary considerably, ranging from 10% to 80%. Menadione and its water-soluble derivatives can be absorbed even in the absence of bile and enter the bloodstream directly. In rats fed a vitamin K-deficient diet, 18 hours after intracardiac injection of (3)H-menadione, 78% of the (3)H was excreted in the urine, 3% in the feces, and 29% remained in the animal. In dogs, bile excretion was observed; 12 hours after oral administration of (14)C-menadione, 5-10% of the (14)C was excreted via this route. Vitamin K accumulates in the liver, spleen, and lungs. However, large amounts of vitamin K3 are not stored in the body for extended periods. Veterinarian: …Absorbed menadione (vitamin K3) is converted to vitamin K2 for use, or it is rapidly excreted in the urine.
Pharmacokinetics of menadione (vitamin K3)... was studied in rabbits after intravenous administration of 75 mg menadione sodium phosphate (Synkayvite). ... Plasma clearance was 0.822 L/min. Erythrocyte clearance was 0.407 L/min. Apparent volume of distribution in plasma was 30.833 L, and in erythrocytes it was 20.488 L. The area under the plasma concentration-time curve was 32.453 μg·min/ml, and in erythrocytes it was 67.219 μg·min/ml. /Menadione sodium diphosphate/

---

Metabolism/Metabolites
Liver
Distribution of tritium-labeled menadione ((3)H(6,7))-2-methyl-1,4-naphthoquinone in rats showed that the lipophilic metabolite of menadione, menadione-4,2-methyl-3-geranylgeranyl-1,4-naphthoquinone, was present in all tissues tested.
2-Methyl-1,4-naphthoquinone produces vitamin K2 (20) in rats; it may produce vitamin K2 (45) and vitamin K2 (50) in humans. /Excerpt from Table/
...Exogenous substances reduced by carbonyl reductases include...menadione....
Menadione is partially excreted as a glucuronide and competes with bilirubin for limited detoxification mechanisms in newborns.
For more metabolite/metabolite (complete) data on menadione (6 metabolites in total), please visit the HSDB record page.
Hepatic

---

Biological Half-Life
Pharmacokinetic studies of menadione (vitamin K3) were conducted in rabbits following intravenous administration of 75 mg menadione diphosphate sodium (Synkayvite). The mean elimination half-life of menadione in plasma was 27.17 min, and the mean elimination half-life in erythrocytes was 35.22 min. /Menadione diphosphate sodium/

Toxicity Summary
Menadione (vitamin K3) participates as a cofactor in the post-translational γ-carboxylation of certain protein glutamate residues in the body. These proteins include vitamin K-dependent coagulation factors II (prothrombin), VII (prothrombin convertase), IX (Christmas factor), X (Stuart factor), protein C, protein S, protein Zv, and growth arrest-specific factor (Gas6). Unlike other vitamin K-dependent proteins in the blood coagulation cascade, protein C and protein S have anticoagulant effects. Two vitamin K-dependent proteins found in bone are osteocalcin (also known as bone G1a (γ-carboxyglutamate) protein or BGP) and matrix G1a protein (MGP). γ-carboxylation is catalyzed by vitamin K-dependent γ-carboxylases. The reduced form of vitamin K, namely vitamin K hydroquinone, is the true cofactor of γ-carboxylases. Proteins containing γ-carboxyglutamate are called G1a proteins. Interactions High doses of salicylates… antagonize vitamin K. ...The compound with antagonistic activity is sulfaquinoline, a sulfonamide drug used in veterinary medicine... /Vitamin K/
Vitamin K antagonism/acetocoumarin, phenylpropargyl, anisole, benzophenone, and phenylindanone/Inhibition of vitamin K-dependent clotting protein synthesis in the liver... /Vitamin K/

---

Non-human toxicity values
Oral LD50 in mice: 500 mg/kg
Intraperitoneal LD50 in mice: 50 mg/kg
Intraperitoneal LD50 in rats: 75 mg/kg
Subcutaneous LD50 in mice: 138 mg/kg

Therapeutic Uses
For a long time, it has been believed that synthetic water-soluble vitamin K (menadione, menadiol) is less effective than vitamin K1 (plant-derived menadione) in treating drug-induced hypoprothrombinemia. Menadione (vitamin K3) is a redox cyclic quinone and an important chemotherapeutic agent in clinical practice. … Menadione, or vitamin K3 (VK3), is a potent oxidative stress inducer and has recently been used as an effective and highly safe cytotoxic drug for the treatment of various human cancers. … Drug Warnings …May not be given to newborns or women in the last few weeks of pregnancy. Menadione is ineffective in treating warfarin and super-warfarin poisoning. It is ineffective and should not be used. Vitamin K (SRP: plant-derived menadione is preferred) must be used with caution in patients who have already received anticoagulant therapy to prevent intravascular thrombosis. … Vitamins must be “tied” according to the dose of the anticoagulant to avoid exposing the patient to the risk of thrombosis that initially led to anticoagulant therapy. There is no such problem for patients poisoned by accidental or suicidal ingestion of anticoagulant rodenticides. There is no evidence that vitamin K causes any excessive blood clotting tendency in normal individuals. Vitamin K
Menadione…can cause hemolysis in patients with glucose-6-phosphate dehydrogenase gene defects.
For more drug warnings (full) data on menadione (6 of 6), please visit the HSDB record page.

---

Pharmacodynamics
Menadione (vitamin K3) is a fat-soluble vitamin precursor that is converted to menadione in the liver. Vitamin K1 and K2 are naturally occurring types of vitamin K. The former, also known as chloroquinone, is synthesized by plants and found in foods such as spinach, broccoli, lettuce, and soybeans. The latter, sometimes called menadione, is mainly produced by bacteria in the foregut and small intestine. On the other hand, vitamin K3 is one of several synthetic vitamin K compounds. This pale yellow synthetic crystalline substance, also known as menadione, is converted to the active form, vitamin K2, in animals. Vitamin K deficiency can be dangerous, especially for infants prone to severe bleeding, but overdose is equally harmful. Newborns who take excessive amounts of vitamin K3 may develop kernicterus, a serious brain injury that can lead to reduced activity, loss of appetite, seizures, deafness, intellectual disability, and even death. This condition is associated with abnormally high concentrations of bilirubin (a bile pigment) in brain tissue, and the presence of vitamin K3 can cause elevated bilirubin levels. Therefore, the medical use of vitamin K3 is not as widespread as it once was.

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.

---

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.

---

View More

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.

---

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