Feierman D E
Department of Anesthesiology, Mount Sinai School of Medicine, City University of New York, New York, USA.
Anesth Analg. 1996 May;82(5):936-41. doi: 10.1097/00000539-199605000-00008.
The metabolism of fentanyl was investigated using rat liver microsomes to determine whether fentanyl is metabolized by rat liver microsomal cytochrome P450 and, if so, which isoform is responsible for the metabolism. Microsomes isolated from rats pretreated with phenobarbital were more active in metabolizing fentanyl than were microsomes from saline controls. The major metabolic pathway of fentanyl was an oxidative N-dealkylation to norfentanyl, which was detected by a gas chromatograph-mass selective detector (GC-MSD) method. The apparent Vm values for microsomes isolated from saline- and phenobarbital-treated rats were 2 and 9 nmol norfentanyl.min-1.mg-1 microsomal protein, and the apparent Km values were 32 and 47 microM, respectively. Fentanyl metabolism was inhibited by antibodies specific for CYP3A1/2, as well as by chemical inhibitors specific for CYP3A. These results indicate that CYP3A1/2 plays a major role in the oxidation of fentanyl to norfentanyl by rat liver microsomes.
利用大鼠肝微粒体研究了芬太尼的代谢情况，以确定芬太尼是否由大鼠肝微粒体细胞色素P450代谢，若如此，哪种同工酶负责该代谢过程。从用苯巴比妥预处理的大鼠中分离出的微粒体在代谢芬太尼方面比生理盐水对照组的微粒体更具活性。芬太尼的主要代谢途径是氧化N-去烷基化生成去甲芬太尼，这是通过气相色谱-质量选择检测器（GC-MSD）方法检测到的。从生理盐水处理组和苯巴比妥处理组大鼠中分离出的微粒体的表观Vm值分别为2和9 nmol去甲芬太尼·min⁻¹·mg⁻¹微粒体蛋白，表观Km值分别为32和47 μM。芬太尼代谢受到CYP3A1/2特异性抗体以及CYP3A特异性化学抑制剂的抑制。这些结果表明，CYP3A1/2在大鼠肝微粒体将芬太尼氧化为去甲芬太尼的过程中起主要作用。
