Vervoort J, Rietjens I M, Moonen C T, von Kienlin M, Despres D
Department of Biochemistry, Agricultural University, Wageningen. The Netherlands.
NMR Biomed. 1991 Dec;4(6):255-61. doi: 10.1002/nbm.1940040602.
The present study describes results from an in vivo 19F NMR study on rats exposed to the xenobiotic compound 2-fluoroaniline. Qualitative pharmacokinetics and the biotransformation of 2-fluoroaniline were studied after exposure to 50 mg/kg body wt 2-fluoroaniline. Accumulation and elimination of the parent compound in and from the liver of exposed animals were readily observed. Metabolites formed in the liver were shown to be efficiently excreted from the liver, as the amount of metabolites in this organ was always less than 10% of the maximum amount of the parent compound observed. In the bladder, rapid accumulation of 2-fluoroaniline-derived metabolites was detected. The metabolite pattern was shown to change in time, with the parent compound being dominantly present during the first hours of exposure. N-acetylated products (4-acetamido-3-fluorophenyl sulphate and 4-acetamido-3-fluorophenyl glucuronide) were observed to accumulate more slowly in the bladder than the non-acetylated products (4-amino-3-fluorophenyl sulphate and 4-amino-3-fluorophenyl glucuronide). Urine metabolite patterns obtained from the bladder in vivo were compared to those obtained during metabolic cage experiments.
本研究描述了对暴露于外源性化合物2-氟苯胺的大鼠进行的体内19F核磁共振研究结果。在给予50mg/kg体重的2-氟苯胺后，研究了其定性药代动力学和生物转化情况。在暴露动物的肝脏中很容易观察到母体化合物的蓄积和消除。肝脏中形成的代谢物被证明能有效地从肝脏排出，因为该器官中代谢物的量始终小于所观察到的母体化合物最大量的10%。在膀胱中，检测到2-氟苯胺衍生代谢物的快速蓄积。代谢物模式随时间变化，在暴露的最初几个小时内母体化合物占主导地位。观察到N-乙酰化产物（4-乙酰氨基-3-氟苯基硫酸盐和4-乙酰氨基-3-氟苯基葡糖醛酸）在膀胱中的蓄积比未乙酰化产物（4-氨基-3-氟苯基硫酸盐和4-氨基-3-氟苯基葡糖醛酸）更慢。将体内从膀胱获得的尿液代谢物模式与代谢笼实验中获得的模式进行了比较。
