Sylvia L A, Gerig J T
Department of Chemistry, University of California-Santa Barbara 93106.
Drug Metab Dispos. 1993 Jan-Feb;21(1):105-13.
High-resolution and surface coil fluorine-19 NMR spectroscpies have been used to study the metabolism of the liver inducer 3-trifluoromethyl-alpha-ethylbenzhydrol (flumecinol) in rats. Although the fluorine chemical shift range exhibited by metabolites is small, it is possible to identify a number of metabolites or classes of metabolites by direct examination of urine samples. 3-Trifluoromethyl-4'-hydroxy-alpha-ethylbenzhydrol was confirmed as the primary metabolite at low doses (42 mg/kg). At higher doses other metabolites characterized by ring and side chain hydroxylation or further oxidation of the parent compound become apparent. NMR evidence for two previously unrecognized metabolites is described but these structures have not been identified. Studies of liver induction are reported that show that a single large dose of flumecinol exerts a substantial inducing effect on the number and types of metabolites formed after several hours postingestion. Examination of liver metabolism of the drug in vivo showed a single broad resonance, and it was not possible to obtained resolved signals for individual metabolites under the conditions of these experiments. However, nuclear Overhauser experiments showed that the materials detected in the in vivo experiments do not interact significantly with the macromolecular components of the liver.
高分辨率和表面线圈氟-19核磁共振光谱已被用于研究肝脏诱导剂3-三氟甲基-α-乙基二苯甲醇（氟美西诺）在大鼠体内的代谢情况。尽管代谢产物所表现出的氟化学位移范围较小，但通过直接检测尿液样本，仍有可能鉴定出多种代谢产物或代谢产物类别。在低剂量（42毫克/千克）时，3-三氟甲基-4'-羟基-α-乙基二苯甲醇被确认为主要代谢产物。在较高剂量时，以母体化合物的环和侧链羟基化或进一步氧化为特征的其他代谢产物变得明显。文中描述了两种先前未被识别的代谢产物的核磁共振证据，但这些结构尚未确定。报告了肝脏诱导研究，结果表明，单次大剂量的氟美西诺在摄入数小时后对所形成的代谢产物的数量和类型具有显著的诱导作用。对该药物在体内的肝脏代谢进行检查时，显示出单一的宽共振峰，在这些实验条件下，无法获得各个代谢产物的分辨信号。然而，核Overhauser实验表明，在体内实验中检测到的物质与肝脏的大分子成分没有明显相互作用。
