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为评价氧氟沙星 ( OFLX)对映体葡醛酸化代谢的立体选择性 ,采用手性 HPLC法测定大鼠肝微粒体孵育液中 OFLX对映体 .结果显示 :经苯巴比妥 ( PB)和β-萘黄酮 ( BNF)诱导的不同葡醛酸转移酶 ( UDPGT)亚族对 OFLX对映体葡醛酸化代谢有不同的影响 .在所试验的对照 ,PB或 BNF诱导的微粒体中 S- ( - ) -和 R- ( + ) - OFLX之间 ,Km 和Vmax无显著性差异 ;但 PB组中 S- ( - ) -和 R- ( + ) -OFLX的 Km 和 Vmax与对照组或 BNF组相应的对映体比较有显著性差异 ;OFLX对映体之间的 Clint在对照组与 BNF组没有显著性差异 ;而在 PB组则有显著性差异 .另外 BNF组的 Clint较对照组和 PB组分别有显著性差异 .因此 ,经 PB诱导的 UDPGT亚族对 S-和 R- OFLX的 相代谢存在立体选择性 ,并主要是由于其催化部位的差异引起了内在清除率的变化 .
To evaluate the stereoselectivity of enrofloxacin metabolism of ofloxacin (OFLX), chiral HPLC was used to determine OFLX enantiomers in rat liver microsomal incubation.The results showed that the phenobarbital ) And β-naphthoflavone (BNF) -induced different glucuronosyltransferase (UDPGT) subunits have different effects on OFLX enantiomeric glucuronidation metabolism.In the control, PB or BNF-induced microsomes tested There were no significant differences in Km and Vmax between S- (-) - and R- (+) - OFLX. However, Km and Vmax of S- (-) - and R- Or BNF group corresponding enantiomers were significantly different; OFLX enantiomer Clint between the control group and the BNF group no significant difference, while in the PB group there was a significant difference.In addition BNF group Clint compared with the control There was significant difference between PBG group and PB group.Therefore, the PBG-induced UDPGT subfamily stereoselective the S- and R-OFLX phase metabolism, and mainly due to the change of its intrinsic clearance caused by the difference of its catalytic site .