Menatetrenone

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Menatetrenone
Structural formula of menatetrenone
Space-filling model of the menatetrenone molecule
Clinical data
Other names3-methyl-2-[(2Z,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraenyl]naphthalene-1,4-dione
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
  • none
Identifiers
  • 2-methyl-3-[(2Z,6E,10E)-3,7,11,15-tetramethylhexadeca-2,6,10,14-tetraen-1-yl]naphthoquinone
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC31H40O2
Molar mass444.648 g/mol g·mol−1
3D model (JSmol)
  • CC1=C(C(=O)C2=CC=CC=C2C1=O)C/C=C(\C)/CC/C=C(\C)/CC/C=C(\C)/CCC=C(C)C
  • InChI=1S/C31H40O2/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/h7-8,12,14,16,18-20H,9-11,13,15,17,21H2,1-6H3/b23-14+,24-16+,25-20+ ☒N
  • Key:DKHGMERMDICWDU-GHDNBGIDSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Menatetrenone (INN), also known as MK-4, is a vitamin K compound used as a hemostatic agent, and also as adjunctive therapy for the pain of osteoporosis. Menatetrenone is one of the nine forms of vitamin K2.[1]

MK-4 is produced via conversion of vitamin K1 in the body, in the testes, pancreas and arterial walls.[2] While major questions still surround the biochemical pathway for the transformation of vitamin K1 to MK-4, studies demonstrate the conversion is not dependent on gut bacteria, occurring in germ-free rats[3][4] and in parenterally-administered K1 in rats.[5][6] In fact, tissues that accumulate high amounts of MK-4 have a remarkable capacity to convert up to 90% of the available K1 into MK-4.[3][4]

Dose

Bioavailability studies have shown that small oral doses are not detected in the blood - for example 420mcg of Menatetrenone or less tested over minutes and hours are not detectable[7], and larger doses in the order of milligrams are required, unlike Vitamin K2 MK7 which is detectable in the blood in mcg doses. Furthermore, as quoted in citation [8] "Administered daily doses of 15, 45, 90, and 135 mg revealed that 45 mg was the minimum effective dose for improving bone mass parameters evaluated by microdensitometry and/or single photon absorptiometry in postmenopausal women with osteoporosis." The study referenced is available in Japanese[9][10]. Briefly, 15mg, 45mg, 90mg, 135mg and a 5th group with 0.75ug of alfacalcidol were evaluated. The counts of people who had a 'moderate improvement' or greater were recorded. The 15mg group had 26.9%, the 45mg 46%, the 90mg 49% and the 135mg had 50.9% of subjects with a moderate improvement or greater.. It was therefore determined that doses above 45mg as much as 135mg have the same effectiveness as 45mg and that 45mg was much better than 15mg. Therefore 45mg was determined to be the ideal dose.

MK-4 is marketed for the osteoporosis indication in Japan by Eisai Co., under the trade name Glakay.

See also

References

  1. ^ Iwamoto J, Takeda T, Sato Y (December 2006). "Menatetrenone (vitamin K2) and bone quality in the treatment of postmenopausal osteoporosis". Nutr. Rev. 64 (12): 509–17. doi:10.1111/j.1753-4887.2006.tb00184.x. PMID 17274493.
  2. ^ Shearer, Shearer MJ; Newman P. (2008). "Metabolism and cell biology of vitamin K". Thrombosis and Haemostasis. 100 (10): 530–547. doi:10.1160/TH08-03-0147. PMID 18841274.
  3. ^ a b Davidson, RT; Foley AL; Engelke JA; Suttie JW (1998). "Conversion of Dietary Phylloquinone to Tissue Menaquinone-4 in Rats is Not Dependent on Gut Bacteria1". Journal of Nutrition. 128 (2): 220–223. doi:10.1093/jn/128.2.220. PMID 9446847.
  4. ^ a b Ronden, JE; Drittij-Reijnders M-J; Vermeer C; Thijssen HHW (1998). "Intestinal flora is not an intermediate in the phylloquinone-menaquinone-4 conversion in the rat". Biochimica et Biophysica Acta (BBA) - General Subjects. 1379 (1): 69–75. doi:10.1016/S0304-4165(97)00089-5. PMID 9468334.
  5. ^ Thijssen, HHW; Drittij-Reijnders MJ (1994). "Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4". British Journal of Nutrition. 72 (3): 415–425. doi:10.1079/BJN19940043. PMID 7947656.
  6. ^ Will, BH; Usui Y; Suttie JW (1992). "Comparative Metabolism and Requirement of Vitamin K in Chicks and Rats". Journal of Nutrition. 122 (12): 2354–2360. doi:10.1093/jn/122.12.2354. PMID 1453219.
  7. ^ Sato, Toshiro (Nov 12, 2012). "Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women". Nutrition Journal. 11 (93): 93. doi:10.1186/1475-2891-11-93. PMC 3502319. PMID 23140417.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ Iwamoto, J (May 2014). "Vitamin K₂ therapy for postmenopausal osteoporosis". Nutrients. 6 (16): 1971–80. doi:10.3390/nu6051971. PMC 4042573. PMID 24841104.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  9. ^ 折茂肇 、藤田拓男 、小野村敏信 (June 1992). "骨粗しょう症に対するメナテトレノン軟カプセル剤(Ea‐0167)の臨床効果 後期第II相用量検討試験". 新薬と臨床. 41 (6): 1249–1279.
  10. ^ "医薬品インタビューフォーム" [Pharmaceutical interview form]. Glakay. Archived from the original on 8 May 2018. Retrieved 5 July 2018.

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