一种新型叶酸盐的口服生物利用度增强：在大鼠药代动力学研究中与叶酸和叶酸钙盐的比较。

Enhanced oral bioavailability of a novel folate salt: comparison with folic acid and a calcium folate salt in a pharmacokinetic study in rats.

作者信息

Miraglia Niccolò, Agostinetto Marco, Bianchi Davide, Valoti Ermanno

机构信息

Gnosis S.p.A., Desio, Monza Brianza, Italy -

出版信息

Minerva Ginecol. 2016 Apr;68(2):99-105.

PMID:27008238

Abstract

BACKGROUND

Folates play an important role to prevent neurological disorders in embryo development and in cardiovascular diseases. Folate supplementation is suggested, particularly in females of childbearing age, for the prevention of embryonal NTDs during pregnancy. Folic acid and reduced folate ((6S)5-MTHF) are currently used in supplementation. The aim of this study was to compare the bioavailability of Quatrefolic®, a novel patented (6S)5-MTHF glucosamine salt, with (6S)5-MTHF calcium salt and folic acid in Sprague Dawley rats.

METHODS

Fifty-four to fifty-five-day old male Sprague-Dawley rats were divided in 3 treatment groups, each comprising 6 animals, receiving folic acid, (6S)5-MTHF calcium salt or Quatrefolic® at the dose of 70 µg/kg of (6S)5-MTHF equivalents in a single oral administration. Folates were determined in plasma with a HPLC method employing fluorimetric detection. (6S)5-MTHF level was chosen as a convenient end point to evaluate folate absorption. The main pharmacokinetic parameters were calculated (Cmax, tmax, AUC).

RESULTS

Quatrefolic® administration produced a plasmatic (6S)5-MTHF concentration peak (Cmax: 879.6±330.3 ng/mL) 1.8 times higher than (6S)5-MTHF Ca salt (486.8±184.1 ng/mL), and 3.1 times higher than folic acid supplementation (281.5±135.7 ng/mL), while tmax values were similar for the three folate forms. Quatrefolic® supplementation showed AUC8h (1123.9 ng/mL ∙ h) 9.7 times higher than folic acid (114.7 ng/mL ∙ h) and 1.12 times higher than (6S)5-MTHF Ca salt (997.6 ng/mL ∙ h).

CONCLUSIONS

Quatrefolic® has demonstrated an enhanced oral bioavailability in comparison to other reduced folates and to folic acid in rats.

摘要

背景

叶酸在预防胚胎发育过程中的神经系统疾病以及心血管疾病方面发挥着重要作用。建议补充叶酸，尤其是在育龄女性中，以预防孕期胚胎神经管缺陷。目前补充剂中使用的是叶酸和还原型叶酸（(6S)5 - 甲基四氢叶酸）。本研究的目的是比较新型专利产品Quatrefolic®（一种(6S)5 - 甲基四氢叶酸葡糖胺盐）与(6S)5 - 甲基四氢叶酸钙盐和叶酸在Sprague Dawley大鼠中的生物利用度。

方法

将54至55日龄的雄性Sprague - Dawley大鼠分为3个治疗组，每组6只动物，以70 μg/kg的(6S)5 - 甲基四氢叶酸当量单次口服给予叶酸、(6S)5 - 甲基四氢叶酸钙盐或Quatrefolic®。采用荧光检测的高效液相色谱法测定血浆中的叶酸。选择(6S)5 - 甲基四氢叶酸水平作为评估叶酸吸收的便捷终点。计算主要药代动力学参数（Cmax、tmax、AUC）。

结果

给予Quatrefolic®后血浆(6S)5 - 甲基四氢叶酸浓度峰值（Cmax：879.6±330.3 ng/mL）比(6S)5 - 甲基四氢叶酸钙盐（486.8±184.1 ng/mL）高1.8倍，比补充叶酸（281.5±135.7 ng/mL）高3.1倍，而三种叶酸形式的tmax值相似。补充Quatrefolic®后的AUC8h（1123.9 ng/mL ∙ h）比叶酸（114.7 ng/mL ∙ h）高9.7倍，比(6S)5 - 甲基四氢叶酸钙盐（997.6 ng/mL ∙ h）高1.12倍。