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吡喹酮(PQT)对映异构体在未诱导大鼠肝微粒体内仅(-)PQT生成一个主要代谢产物-RingD-OH,而在β-萘黄酮(β-NF)诱导的大鼠肝微粒体内两者均生成RingD-OH.(+)PQT在苯巴比妥(PB)诱导的肝微粒体内可生成三个主要代谢物,即RingD-OH,RingB-OH和RingA-OH,而(-)PQT仅生成RingD-OH和RingA-OH.在地塞米松(DEX)诱导的大鼠肝微粒体内,PQT对映异构体代谢后生成四个主要产物,除RingD-OH,RingB-OH和RingA-OH外,尚有RingD,B-2OH.PQT对映异构体无论在β-NF,PB或DEX诱导的肝微粒体内,RingD-OH的生成速率均为(-)PQT大于(+)PQT,RingB-OH和RingA-OH的生成均为(+)PQT较(-)PQT优先被羟化.本实验结果表明,β-NF,PB和DEX所诱导的CYP1A,CYP2B和CYP3A及未诱导P450代谢PQT对映异构体表现出完全的或部分的立体选择性.
The PQT enantiomer produced only one (-) PQT-only major metabolite, RdD-OH, in uninduced rat liver microsomes, whereas in the β-naphthoflavone (β-NF) RingD-OH is formed in both microsomes. (+) PQT generated three main metabolites, RingD-OH, RingB-OH and RingA-OH, in phenobarbital-induced liver microsomes while (-) PQT produced only RingD-OH and RingA -OH. In dexamethasone (DEX) -induced rat liver microsomes, PQT enantiomers were metabolized to produce four major products, in addition to RingD-OH, RingB-OH and RingA-OH, there RingD, B-2OH . The formation rate of RingD-OH was (-) PQT was greater than (+) PQT and the formation of RingB-OH and RingA-OH were both in the PQT enantiomer in either β-NF, PB or DEX-induced liver microsomes (+) PQT is (-) PQT preferentially hydroxylated. The results of this experiment show that β-NF, PB and DEX-induced CYP1A, CYP2B and CYP3A and un-induced P450 metabolic PQT enantiomers showed complete or partial stereoselectivity.