转运蛋白基因多态性与利培酮分布的相关性研究

 目的 研究中国汉族健康志愿者利培酮人体代谢过程与其主要转运蛋白基因多态性的关系。方法 23名健康志愿者单次口服利培酮2 mg后，用LC-MS/MS测定血中的利培酮及其代谢产物9-羟基利培酮浓度，研究利培酮的药代动力学与其主要转运蛋白P-糖蛋白和乳腺癌耐药蛋白（BCRP）基因型的相关性。结果 BCRP 421CA/34GA基因型携带者的9-羟基利培酮AUC_0-∞和ρ_max分别是其他受试者的66.6%和51.1%，具有显著性差异（P=0.011，P=0.017），BCRP C421A和MDR1 G2677T/A对利培酮t_max均有影响（P<0.05）。结论 BCRP基因型影响9-羟基利培酮的体内代谢分布，BCRP和P-糖蛋白可能同时参与了利培酮的吸收。

Correlation of Genetic Polymorphism of Transporter with Resperidone Metabolism

OBJECTIVE To study the relationship between the genetic polymorphisms of the main transporter of risperidone and its pharmacokinetics in Chinese healthy volunteers.METHODS 2 mg of risperidone was orally administered to 23 healthy Chinese subjects,and blood samples were taken after dosing.The polymorphic alleles of P-glycoprotein(P-gp) and breast cancer resistance protein(BCRP) were determined in each subject.The whole blood concentrations of risperidone and 9-hydroxyrisperidone were measured by high performance liquid chromatography/tandem mass spectrometry(HPLC-MS/MS).RESULTS The AUC0-∞ and ρmax of 9-hydroxyrisperidone in subjects carrying BCRP 421CA/34GA genotype were 66.6% and 51.1%(P=0.011,P=0.017) of other subjects,respectively.The tmax of risperidone was significantly influenced by BCRP C421A and MDR1 G2677T/A(P<0.05).CONCLUSION The disposition of 9-hydroxyrisperidone was affected by BCRP genetic polymorphisms.P-gp and BCRP genotype may also play a role in risperidone absorption.