Folic acid and its metabolite codetermination for pharmacokinetics with circadian rhythms and evaluation of oral bioavailability

doi:10.1111/jphp.13155

	Folic acid and its metabolite codetermination for pharmacokinetics with circadian rhythms and evaluation of oral bioavailability
	Meng, Fanyue 1,2; Zhang, Guoqing 1,2; Wang, Caifen 1; Zhu, Rui 2; Li, Haiyan 1; Xu, Jian 1,3; Shakya, Shailendra 1,3; Chen, Weidong 2; Wu, Li 1; Zhang, Jiwen 1,2,3
刊名	JOURNAL OF PHARMACY AND PHARMACOLOGY
	2019-08-21
页码	10
关键词	5-methyltetrahydrofolic acid circadian rhythms fasted plasma folic acid pharmacokinetics
ISSN号	0022-3573
DOI	10.1111/jphp.13155
通讯作者	Chen, Weidong(anzhongdong@126.com) ; Wu, Li(track_wuly@163.com) ; Zhang, Jiwen(jwzhang@simm.ac.cn)
英文摘要	Objectives Pharmacokinetics of vitamins is still a challenge. In this study, folic acid (FA) was used as a model drug and aimed at investigating a reliable method for its detailed pharmacokinetic evaluations. Methods An high-performance liquid chromatography-tandem mass spectrometry method was developed and performed to determinate the FA and 5-methyltetrahydrofolic acid (5-methylTHF) simultaneously, which was applied to characterize the circadian rhythms as well as the pharmacokinetics of different preparations. Key findings The plasma concentration of 5-methylTHF in fasted state was twofold higher than that in fed state. The circadian rhythms were studied before the pharmacokinetics and revealed that free FA was almost undetected in blank plasma, while 5-methylTHF had a slight decrement at 12:00. Hence, the pharmacokinetics of FA was conducted and showed that the administration of FA solution resulted in enhancing bioavailability of 5-methylTHF comparing with FA raw material suspension, whereas the free FA level in plasma was similar. The mechanism could be that FA was rapidly metabolized to 5-methylTHF in intestinal epithelial cell after absorption, which revealed that intestinal metabolism would affect its bioavailability. Conclusion A suitable method was established considering the baseline level, circadian rhythms and intestinal metabolism to investigate the pharmacokinetics of FA for guiding the further research of vitamins.
资助项目	National Science and Technology Major Projects for New Drugs Innovation and Development[2017ZX09101001-005] ; Intergovernmental Key International Scientific and Technological Innovation Cooperation[2016YFE0125100] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050307]
WOS关键词	LIQUID-CHROMATOGRAPHY ; 5-METHYLTETRAHYDROFOLIC ACID ; HUMAN PLASMA ; MASS-SPECTROMETRY ; FOLATE ; HOMOCYSTEINE ; SUPPLEMENTATION ; QUANTITATION ; ASSOCIATION ; EXTRACTION
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	WILEY
WOS记录号	WOS:000482852300001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288793]
专题	中国科学院上海药物研究所
通讯作者	Chen, Weidong; Wu, Li; Zhang, Jiwen
作者单位	1.Chinese Acad Sci, Shanghai Inst Materia Med, Ctr Drug Delivery Syst, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Anhui Univ Chinese Med, Sch Pharmaceut Sci, Inst Drug Metab, 1 Qianjiang Rd, Hefei 230012, Anhui, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Meng, Fanyue,Zhang, Guoqing,Wang, Caifen,et al. Folic acid and its metabolite codetermination for pharmacokinetics with circadian rhythms and evaluation of oral bioavailability[J]. JOURNAL OF PHARMACY AND PHARMACOLOGY,2019:10.
APA	Meng, Fanyue.,Zhang, Guoqing.,Wang, Caifen.,Zhu, Rui.,Li, Haiyan.,...&Zhang, Jiwen.(2019).Folic acid and its metabolite codetermination for pharmacokinetics with circadian rhythms and evaluation of oral bioavailability.JOURNAL OF PHARMACY AND PHARMACOLOGY,10.
MLA	Meng, Fanyue,et al."Folic acid and its metabolite codetermination for pharmacokinetics with circadian rhythms and evaluation of oral bioavailability".JOURNAL OF PHARMACY AND PHARMACOLOGY (2019):10.