多药耐药基因多态性对利培酮及9-羟基利培酮稳态血药浓度的影响

Influence of multidrug resistence genes 1 polymorphisms on the steady-state plasma concentration of risperidone and 9-hydroxyrisperidone

多药耐药基因(MDR1)是跨膜转运体P-糖蛋白(P-gp)的编码基因。胃肠道和血脑屏障等组织中的P-gp可以将包括药物在内的外源性底物排出细胞,影响P-gp底物药物的吸收和分布。MDR1基因多态性会影响P-gp表达和活性,进而影响底物药物的血药浓度和临床疗效,非典型性抗精神药物利培酮及代谢物9-羟基利培酮都是P-gp底物,MDR1基因多态性与这类药物的血药浓度和临床疗效可能相关。

Multidrug resistence genes 1 （ MDR1 ） encodes the transmem- brahe transporter P - glycoprotein（ P - gp）. P - gp is widely expressed in human tissues. It can pump exogenous substrates out of cells and there- fore may limit the absorption and distribution of drugs which are the sub- strates of P - gp. MDR1 gene polymorphisms effect plasma concentrations and clinical responses through regulating expression and activity of P - gp. MDR1 gene polymorphisms may influence the plasma concentration of atypical antipsychotic drug risperidone and its metabolites （9 - hydroxyresperidone）. Because both are substrates of P- gp. This review the influence of MDR1 gene polymorphisms on plasma concentrations of risperidone and 9 -hydroxyrisperidone.