Stereoselectivity in renal clearance of trans -tramadol and its active metabolite, trans-O- demethyltramadol  

反式曲马朵及其活性代谢产物反式氧去甲基曲马朵肾脏清除的立体选择性(英文)

作　　者：刘会臣[1] 张熙洁 杨燕燕[1] 王娜[1] 侯艳宁[1] 

机构地区：[1]白求恩国际和平医院临床药理室,石家庄050082 [2]唐山妇幼医院药剂科,唐山中国063000

出　　处：《Acta Pharmacologica Sinica》2002年第1期85-88,共4页中国药理学报（英文版）

摘　　要：enantiomer being preferentially cleared into the urine.To study the stereoselectivity in renal clearance of trans-tramadol and its active metabolite, trans-O-demethyltramadol. METHODS: The right kidneys were isolated from male SD rats and perfused with 100 mL of perfusate medium containing trans-tramadol 300 μg/L or trans-O-demethyltramadol 50 μg/L. After perfusion, the concentrations of the enantiomers of trans-tramadol and trans-O-demethyltramadol in the perfusate and urine were determined by high perfonnance capillary electrophoresis. The enantiomeric ratios were calculated. RESULTS: After the kidneys being perfused with /ram-tramadol hydrochloride, the concentration of (+)-trans-tramadol was higher than that of (-)-rrara-tramadol, and the concentration of (+)-trans-O-demethyltramadol was lower than that of (-)-trans-O-demethyltramadol in the perfusate; meanwhile, (+)-trans-tramadol was more than (-)-trans-tramadol, and (+)-trans-demethyltramadol was less than (-)-trans-0-demethyltramadol in the urine. After the kidneys being perfused with trans-O-demethyltramadol, the concentration of (+)-trans- O-demethyltramadol was lower than that of (-)-trans-O-demethyltramadol in the perfusate, and (+)-trans-O-demethyltramadol was more than (-)-trans-O-demethyltramadol in the urine. CONCLUSION: The renal clearance of trans-tramadol was stereoselective. The O-demethylation of trans-tramadol was stereoselective in the kidneys, (-)- trans -tramadol being preferentially metabolized. The renal clearance of trans-O-demethyltramadol was also stereoselective, the ( + )-目的:研究反式曲马朵及其活性代谢物反式氧去甲基曲马朵肾脏清除的立体选择性.方法:取雄性SD大鼠的右肾,分别以含反式曲马朵(300μg/L)或反式氧去甲基曲马朵(50μg/L)的灌流液(10mL)进行灌流;利用高效毛细管电泳法测定灌流后灌流液、尿液中反式曲马朵及反式氧去甲基曲马朵对映体的浓度,并计算对映体浓度比值.结果:以反式曲马朵进行离体肾灌流后,在灌流液中,(+)-反式曲马朵的浓度高于(-)-反式曲马朵的浓度,(+)-反式氧去甲基曲马朵的浓度低于(-)-反式氧去甲基曲马朵的浓度;在尿液中,(+)-反式曲马朵较(-)-反式曲马朵多,(+)-反式氧去甲基曲马朵较(-)-反式氧去甲基曲马朵少.以反式氧去甲基曲马朵灌流后,在灌流液中(+)-反式氧去甲基曲马朵的浓度低于(-)-反式氧去甲基曲马朵的浓度;在尿液中(+)-反式氧去甲基曲马朵较(-)-反式氧去甲基曲马朵高.结论:反式曲马朵及反式氧去甲基曲马朵的肾脏清除具有立体选择性.在肾脏中反式曲马朵的氧去甲基代谢具有立体选择性,以(-)-反式曲马朵优先代谢成(-)-反式氧去甲基曲马朵.反式氧去甲基曲马朵的尿排泄具有立体选择性,以(+)-反式氧去甲基曲马朵占优.

关 键 词：TRAMADOL KIDNEY PERFUSION stereo-isomerism PHARMACOKINETICS 

分 类 号：R9[医药卫生—药学]