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Aim:To study the metabolism of gambogic acid(GA)and the effects of selectivecytochrome P-450(CYP450)inhibitors on the metabolism of GA in rat liver mi-crosomes in vitro.Methods:Rat liver microsomes were used to perform metabo-lism studies.Various selective CYP450 inhibitors were used to investigate theireffects on the metabolism of GA and the principal CYP450 isofonn involved in theformation of major metabolite M_1 in rat liver microsomes.Types of inhibition in anenzyme kinetics model were used to model the interaction.Results:GA wasrapidly metabolized to two phase I metabolites,M_1 and M_2,in rat liver microsomes.Ml and M_2 were tentatively presumed to be the hydration metabolite and epoxidemetabolite of GA,respectively,α-Naphthoflavone uncompetitively inhibited theformation of M_1 while ketoconazole,sulfaphenazole,diethyl dithiocarbamate andquinidine had little or no inhibitory effects on the formation of M_1.Conclusion:GA is rapidly metabolized in rat liver microsomes and M_1 is crucial for the elimina-tion of GA.Cytochrome P-450 1A2 is the major rat CYP involved in the metabolismof GA.
Aim: To study the metabolism of gambogic acid (GA) and the effects of selective cytochrome P-450 (CYP450) inhibitors on the metabolism of GA in rat liver mi-crosomes in vitro. Methods: Rat liver microsomes were used to perform metabo- lism studies.Various selective CYP450 inhibitors were used to investigate the effects of the metabolism of GA and the principal CYP450 isofonn involved in the formation of major metabolite M_1 in rat liver microsomes.Types of inhibition in anenzyme kinetics model were used to model the interaction. Results: GA wasrapidly metabolized to two phase I metabolites, M_1 and M_2, in rat liver microsomes. Ml and M_2 were tentatively presumed to be the hydration metabolite and epoxide metabolite of GA, respectively, α-Naphthoflavone uncompetitively inhibited the formation of M_1 while ketoconazole, sulfaphenazole, diethyl dithiocarbamate andquinidine had little or no inhibitory effects on the formation of M_1. Confluence: GA is rapidly metabolized in rat liver microsomes and M_1 is cr ucial for the elimina- tion of GA.Cytochrome P-450 1A2 is the major rat CYP involved in the metabolism of GA.