Metabolism and effect of para-toluene-sulfonamide on rat liver microsomal cytochrome P450 from in vivo and in vitro studies  

作　　者：Jiang-quan ZHOU Zhi-qiang TANG Jin-nan ZHANG Jing-cheng TANG 

机构地区：[1]Department of Pharmacy, Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021 China [2]School of Chemical Biology and Pharmaceutical Sciences, Capital University of Medical Sciences, Beijing 100069, China

出　　处：《Acta Pharmacologica Sinica》2006年第5期635-640,共6页中国药理学报（英文版）

摘　　要：Aim： To study the in vivo and in vitro metabolism and the effect of para-toluenesulfonamide （PTS） on cytochrome P450 enzymes （CYP450）. Methods： Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver microsomes. Specific CYP isoform activities were determined by using HPLC. CYP chemical inhibitors added to the incubation mixture were used to investigate the principal CYP isoforms involved in PTS metabolism. The effect of PTS on CYP isoforms was investigated by incubating PTS with specific substrates. Results： The groups treated with 33 and 99 mg/kg per d PTS, respectively, had a total CYP content of 0.66±0.17 and 0.60±0.12 nmol/mg. The Km and Vmax were 92.2 μmol/L and 0.0137 nmol/min per mg protein. CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in the rat liver. The inhibitory effects of sulfaphenazole and ketoconazole on PTS metabolism were shown to have a mixed mechanism, whereas PTS metabolism was inhibited noncompetitively by quinidine. PTS had little effect on the activities of the selected CYP isoforms. Conclusion： Generally speaking, it is relatively safe for PTS to be co-administered with other drugs. However, care should be taken when administering PTS with CYP inhibitors and the substrates of CYP2C, CYP2D and CYP3A.Aim： To study the in vivo and in vitro metabolism and the effect of para-toluenesulfonamide （PTS） on cytochrome P450 enzymes （CYP450）. Methods： Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver microsomes. Specific CYP isoform activities were determined by using HPLC. CYP chemical inhibitors added to the incubation mixture were used to investigate the principal CYP isoforms involved in PTS metabolism. The effect of PTS on CYP isoforms was investigated by incubating PTS with specific substrates. Results： The groups treated with 33 and 99 mg/kg per d PTS, respectively, had a total CYP content of 0.66±0.17 and 0.60±0.12 nmol/mg. The Km and Vmax were 92.2 μmol/L and 0.0137 nmol/min per mg protein. CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in the rat liver. The inhibitory effects of sulfaphenazole and ketoconazole on PTS metabolism were shown to have a mixed mechanism, whereas PTS metabolism was inhibited noncompetitively by quinidine. PTS had little effect on the activities of the selected CYP isoforms. Conclusion： Generally speaking, it is relatively safe for PTS to be co-administered with other drugs. However, care should be taken when administering PTS with CYP inhibitors and the substrates of CYP2C, CYP2D and CYP3A.

关 键 词：cytochrome P450 para-toluene-sulfon amide liver microsomes HPLC INHIBITOR 

分 类 号：R575[医药卫生—消化系统]