Leurs R, Donnell D, Timmerman H, Bast A
Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands.
J Pharm Pharmacol. 1987 Oct;39(10):835-7. doi: 10.1111/j.2042-7158.1987.tb05127.x.
NADPH-catalysed biotransformation of nefopam in liver microsomes obtained from phenobarbitone-pretreated rats leads to the formation of an inactive cytochrome P450 metabolic intermediate (MI) complex. This complex can be detected spectrophotometrically by an absorbance maximum at 459 nm. The extent of the in-vitro MI complexation of 33 microM nefopam, a cyclic analogue of orphenadrine, was almost equal to the extent of the in-vitro MI complexation of 33 microM tofenacine, the mono-N-demethylated metabolite of orphenadrine. The time course of the MI complexation of nefopam and studies with two of its major metabolites suggest an initial biotransformation, which has to occur before MI complexation can take place. Maximal MI complexation of nefopam occurred at approximately 25 microM, whereas the MI complexation could not be detected at 100 microM nefopam.
在从苯巴比妥预处理大鼠获得的肝微粒体中，NADPH催化的奈福泮生物转化导致形成无活性的细胞色素P450代谢中间体（MI）复合物。该复合物可通过459nm处的最大吸光度进行分光光度法检测。33μM奈福泮（邻甲苯海明的环状类似物）的体外MI络合程度几乎与33μM托非那辛（邻甲苯海明的单N-去甲基代谢物）的体外MI络合程度相等。奈福泮MI络合的时间进程及其两种主要代谢物的研究表明，在MI络合发生之前必须先进行初始生物转化。奈福泮的最大MI络合发生在约25μM时，而在100μM奈福泮时未检测到MI络合。
