大鼠肝微粒体细胞色素P4503A参与吡喹酮A环羟化代谢

INVOLVEMENT OF CYTOCHROME P4503A IN THE MONOHYDROXYLATION OF RING A OF PRAZIQUANTEL IN RAT LIVER MICROSOMES

三乙酰竹桃霉素（ＴＡＯ）可使地塞米松（ＤＥＸ）诱导的大鼠肝微粒体内未结合细胞色素Ｐ４５０（Ｐ４５０）含量降低，红霉素（ＥＲＹ）和乙基吗啡（ＥＭＰ）Ｎ脱甲基酶活性降低和吡喹酮（ＰＺＱ）Ａ环一羟化物生成速率降低。ＴＡＯ和ＥＲＹ对ＰＺＱＡ环一羟化物的生成表现为竟争性抑制，且ＰＺＱＡ环一羟化物生成速率与ＥＲＹ，ＥＭＰＮ脱甲基酶活性高度相关。结果表明，Ｐ４５０３Ａ（ＣＹＰ３Ａ）参与了ＰＺＱＡ环的羟化。

The possibility of involvement of cytochrome P4503A(CYP3A) in the monohydroxylation of the ring A of praziquantel(PZQ) was studied by using CYP3A specific inducer dexamethasone(DEX), specific inhibitor triacetyloeandomycin(TAO) and the activity of erythromycin(ERY) and ethylmorphine(EMP) N demethylase which are known to be marker for CYP3A enzyme activity as probes. In the liver microsomes obtained from rats pretreated with CYP3A inducer DEX with TAO treatment the content of uncomplexed P450 was decreased, the activity of ERY and EMP N demethylase was reduced, and simultaneously, the rate of formation of ring A monohydroxylate of PZQ was inhibited. Ring A monohydroxylate formation was competitively inhibited by TAO and ERY. The rates of ring A monohydroxylate formation were strongly correlated with the activity of N demethylase of ERY and EMP. These results indicate that CYP3A is involved in the monohydroxylation of the ring A of PZQ.