摘要
硝苯吡啶（Ｎｉｆｅｄｉｐｉｎｅ，ＮＦ）在人肝徽粒体内对（－）－和（＋）－ＰＱＴ的代谢均有竞争性抑制作用，抑制原药消除的Ｋｉ分别为１．４和６．１μｍｏｌ／Ｌ有明显立体选择性，抑制（－）－ＰＱＴＭＩ生成的Ｋｉ为１．５μｍｏｌ／Ｌ；在大鼠肝微粒体内，ＮＦ对（－）－ＰＱＴ代谢的抑制作用远比在人肝微粒体内弱，其抑制（－）－和（＋）－ＰＱＴ原药消除的Ｋｉ分别为１１．６和１０μｍｌ／Ｌ，抑制（－）－ＰＱＴ代谢物生成的Ｋｉ为１０μｍｏｌ／Ｌ。然而，ＮＦ在人肝微粒体内对美多洛尔α－羟化酶和乙基吗啡Ｎ－脱甲基酶几乎无抑制作用，对７－乙氧基香豆素Ｏ－脱乙基酶仅有较弱的抑制作用，说明ＮＦ是ＰＱＴ特别是（－）－ＰＱＴ代谢的特异抑制剂。
ifedipind(NF) competitively and stereoselectively inhibited the metabolism of praziquantel(PQT)enantiomers in human liver microsomes。 Ki value of NF for the(-)-PQT measuredeither by parent drug disappearance of by the MI formation was 1. 4 and 1. 5μmol/L, respec-tively, both of which was much less than the Ki value of 6. 1μmol/L for(+)-PQT measuredby parent drug disappearance. The inhibitory effect of NF on(-)-PQT metabolism in the ratliver microsomes was much less than in human liver microsomes. The Ki value for(-)-PQTand(+)-PQT disappearance were 11.6 and 10. 0μmol/L. and Ki for MI formation from(-)-PQT was 10 μmol/L。 NF had no or a little inhibitory effect on the activities of metoprolol-hy-droxylase, ethylmorphine N-demethylase and 7-ethoxycoumarin O-deethylase. Metoprolol,arepresentative substrate of P450 IID6,had little effect on(-)-PQT and(+)-PQTmetabolism;furthermore,quinidine as a specific inhibitor of P450 IID6 only exhibited a very weakinhibitory effect on(-)-PQT and(+)-PQT metabolim These findings indicated that thepossidility of P450 IID6 involved in the metabolism of PQT enantiomers might be very low.
出处
《重庆医科大学学报》
CAS
CSCD
1995年第3期165-169,共5页
Journal of Chongqing Medical University
关键词
吡喹酮
肝微粒体
硝苯吡啶
细胞色素P450
同功酶
Nifedipine
Enzyme lnhibitor
Human Liver Microsomes
Metabolism
Praziquantel Enantiomers
