Menatetrenone


Menatetrenone, also known as MK-4, is a vitamin K2 subtype which is water soluble and 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.
MK-4 is produced via conversion of vitamin K1 in the body, in the testes, pancreas and arterial walls. 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 and in parenterally-administered K1 in rats. 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.

Dose

Bioavailability studies have shown that small oral doses are not detected in the blood – for example 420 mcg of menatetrenone or less tested over minutes and hours are not detectable, and larger doses in the order of milligrams are required, unlike vitamin K2 MK-7 which is detectable in the blood in mcg doses. Furthermore, "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 also available in Japanese. Briefly, four groups with doses of 15 mg, 45 mg, 90 mg, and 135 mg, and a 5th group with 0.75 mcg of alfacalcidol were evaluated. The counts of people who had a 'moderate improvement' or greater were recorded. The 15-mg group had 26.9%, the 45-mg – 46%, the 90-mg – 49%, and the 135-mg had 50.9% of subjects with a moderate improvement or greater. It was therefore determined that doses above 45 mg as much as 135 mg have the same effectiveness as 45 mg and that 45 mg was much better than 15 mg. Therefore, 45 mg 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.