摘要
应用１９Ｆ体内核磁共振技术（１９ＦＮＭＲ）直接观测了５－氟尿嘧啶（５－ＦＵ）在小鼠肝脏中的代谢产物和代谢动力学，昆明种（ＫＭ）小鼠和Ｃ５７小鼠ｉｖ５－ＦＵ２００ｍｇ·ｋｇ－１后，用１９Ｆ表面线圈测得５－ＦＵ在肝脏中依次代谢为α－氟－β－脲基丙酸（ＦＵＰＡ）和α－氟－β－丙氨酸（ＦＢＡＬ）．在荷Ｓ１８０瘤ＫＭ小鼠肝脏中还可检测到活化产物氟代核苷／核苷酸（ＦＮＵＣ）．５－ＦＵ在ＫＭ和Ｃ５７小鼠肝脏中清除较快，消除半衰期分别为１６．７±３．０和３６．６±２．４ｍｉｎ，其主要产物ＦＢＡＬ的最大生成ｒｍａｘ（相对强度比）分别为８４±１４和９２±１０．但在ＫＭ小鼠肝脏中由ＦＵＰＡ进一步降解为ＦＢＡＬ的速率明显快于Ｃ５７小鼠，ｔ１／２ｒ分别为３１±８和５７±１３ｍｉｎ．相应地，在Ｃ５７小鼠肝脏中ＦＵＰＡ能维持一定的水平并达到ｒｍａｘ２６．２±２．２．
The metabolism of 5 fluorouracil(5 FU) in the livers of Kunming (KM) and C57 mice were serially monitored by in vivo 19 F nuclear magnetic resonance spectroscopy (in vivo 19 F NMR) using surface coil. 19 F NMR spectra were recorded over the certain period at 376.1 MHz after iv bolus of 5 FU (200 mg·kg 1 ). These spectra shown that 5 FU was biotransformed successively to two products, α fluoro β ureidopropionic acid (FUPA) and α fluoro β alanine (FBAL) in the livers of KM and C57 mice. The cytotoxic anabolite, fluorinated nucleosides/tides (FNUC) was found in the liver of a S180 tumor bearing KM mouse. The disappearance of 5 FU from the livers of KM and C57 mice was rapidly with the elimination t 1/2ke of 16.3±3.0 and 36.6±2.4 min, respectively. The maximal formation of the major metabolite FBAL was 84.4±14 (intensity ratio) in the livers of KM mice, and was 91.6±10 in the C57 mice. But the transformation rate of FBAL from FUPA was faster in the livers of KM mice than in that of C57 mice (t 1/2r of 31±8 min vs 57±13 min). Correspondingly, the signal of FUPA disappeared very quickly in the livers of KM mice, and the production of FUPA could be reached to the maximal value of 26.22. The results indicate that the in vivo 19 F NMR can provide a non invasive measurement for the metabolism study in vivo and assessment of efficiency of a fluorinated drug.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
1997年第4期281-285,共5页
Chinese Journal of Pharmacology and Toxicology
关键词
氟尿嘧啶
氟19
NMR
肝脏
药代动力学
fluorouracil
metabolite
pharmacokinetics
in vivo
19 F nuclear magnetic resonance
liver
