Effect of ademetionine on cytochrome P450 isoforms activity in rats

Cocktail method was used to evaluate the influence of ademetionine on the activities of CYP450 isoforms CYP1A2, CYP2D6, CYP3A4, CYP2C19, CYP2C9 and CYP2B6, which were reflected by the changes of pharmacokinetic parameters of six specific probe drugs phenacetin, metroprolol, midazolam, omeprazole, tolbutamide and bupropion, respectively. The experimental rats were randomly divided into two group, control group and ademetionine group. The ademetionine group rats were given 50 mg/kg ademetionine by continuous oral administration for 7 days. The mixture of six probes was given to rats through oral administration and the blood samples were obtained at a series of time-points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by UPLC-MS/MS. In the experiment for ademetionine and control group, there was statistical pharmacokinetics difference for phenacetin, metroprolol, midazolam, omeprazole, tolbutamide and bupropion. Continuous oral administration for 7 days could induce the activities of CYP450 isoforms CYP1A2 of rats, while it may inhibit the activities of CYP2D6, CYP3A4, CYP2C19 and CYP2C9.