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The study of bioavailability and endogenous circadian rhythm of menaquinone-7, a form of vitamin K2, in healthy subjects

Published online by Cambridge University Press:  03 May 2023

Fan Du
Affiliation:
Chonggang General Hospital, Chongqing, People’s Republic of China
Min Yan
Affiliation:
Chongqing Denali Medpharma, Co., Ltd, Chongqing, People’s Republic of China
Lili Duan
Affiliation:
Guangdong Sungen Biotech, Co., Ltd, Shantou, People’s Republic of China
Guolong Xie
Affiliation:
Chonggang General Hospital, Chongqing, People’s Republic of China
Xiuhua Yao
Affiliation:
Chonggang General Hospital, Chongqing, People’s Republic of China
Wenjing Hu
Affiliation:
Chonggang General Hospital, Chongqing, People’s Republic of China
Yu Liu
Affiliation:
Chongqing Denali Medpharma, Co., Ltd, Chongqing, People’s Republic of China
Min Meng*
Affiliation:
Chongqing Denali Medpharma, Co., Ltd, Chongqing, People’s Republic of China
Jiepeng Chen*
Affiliation:
Guangdong Sungen Biotech, Co., Ltd, Shantou, People’s Republic of China
Di Shao*
Affiliation:
Chonggang General Hospital, Chongqing, People’s Republic of China Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, People’s Republic of China
*
*Corresponding authors: Di Shao, email di.shao@cgghcc.com; Jiepeng Chen, email stcjp888@163.com; Min Meng, email min.meng@denalimedpharma.com
*Corresponding authors: Di Shao, email di.shao@cgghcc.com; Jiepeng Chen, email stcjp888@163.com; Min Meng, email min.meng@denalimedpharma.com
*Corresponding authors: Di Shao, email di.shao@cgghcc.com; Jiepeng Chen, email stcjp888@163.com; Min Meng, email min.meng@denalimedpharma.com

Abstract

Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid–liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.

Type
Research Article
Copyright
© The Author(s), 2023. Published by Cambridge University Press on behalf of The Nutrition Society

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Footnotes

These authors contribute equally to this work.

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