Abstract: AIM: To study the gender difference of limonin metabolism and the effects of selective CYP450 inhibitors on the metabolism of limonin in rat liver microsomes.METHODS: Limonin was incubated in rat liver microsomes, the enzyme kinetics parameters were studied; the metabolism of gender differences of limonin in male and female rat liver microsomes were compared; four kinds of CYP450 subtype specificity inhibitors were incubated with liver microsomes, the metabolic inhibition of inhibitors of limonin were calculated.RESULTS: The optimal incubation time was 30 min and the optimal enzyme concentration was 2.0 mg/mL. Km of limonin in female and male rat liver microsomes are (12±3) and (16±4) μg/mL and V_max are (49±6) and (93±14) ng·min^-1·mg^-1. The metabolic percentage are (33.9±4.7)% and (53.8±2.8)% and metabolic rate are(4.46±0.62)and (7.08±0.37) ng·min^-1·mg^-1 respectively in famle and male rat liver microsomes. Inparticularly Ketoconazole(Ket) and Cimetidine (Cime) had significant inhibitory effects on the metabolism of limonin. It was further found that α-Naphthoflavone (α-Naph) and Quinidine (Quin) had little effects on the metabolism of limonin.CONCLUSION: The gender difference of limonin metabolism in rat liver microsomes has been investigated in this study, and the CYP3A2 and CYP2C11 may be the main reason for the sex difference.

Key words: limonin, liver microsome, CYP450, pharmacokinetics, gender difference