[Involvement of cytochrome P4503A in the monohydroxylation of ring A of praziquantel in rat liver microsomes].
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 ws 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.
Department of Pharmacology, Chongqing University of Medical Sciences, Chongqing 630046.
Y J
YJ
Zhang
Y Z
YZ
Quan
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D006900:Hydroxylation; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000378:metabolism; D011223:Praziquantel / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014217:Troleandomycin / Q000494:pharmacology
D065607:Cytochrome P-450 Enzyme Inhibitors; D011223:Praziquantel; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D014217:Troleandomycin; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D005037:Ethylmorphine-N-Demethylase