The Effect Of CYP2D6 Genetic Polymorphisms On The Serum Concentration Of Risperidone And Metabolites

Objective To investigate the effect of cytochrome P4502D6(CYP2D6)gene polymorphism on the plasma concentration of risperidone(RIS)and its metabolite(9-OH-RIS).Methods The RIS and 9-OH-RIS blood concentration detection methods were established by column switching high performance liquid chromatography(CSHPLC)and the standard blood concentration was calculated.Sixty patients with schizophrenia treated with risperidone were randomly selected as subjects,their blood levels were measured and standard plasma concentrations were calculated.The CYP2D6 gene polymorphism was determined by polymerase chain reaction(PCR).The metabolic types of RIS and 9-OH-RIS in patients with depression carrying different gene types were analyzed.Results The CSHPLC detection method of RIS and 9-OH-RIS was successfully established.The standard curve of RIS is: Y = 0.0174X-0.0068,r2 = 0.99782;the standard curve of 9-OH-RIS is Y =0.00047X+0.0018,r2= 0.99958,the minimum detection limit is 3.2 ng·mL-1.Electrophoresis results showed that among 60 patients with schizophrenia,homozygous mutants(CYP2D6*10/*14)were 27 cases,accounting for 45%;hybrids[CYP2D6*1(*2)/*14] were 15 cases.25%,wild-type homozygous [CYP2D6*1(*2)/*5] was 18 cases,accounting for 30%.Cris,C9-OH and C9-OH/Cris were statistically significant among the 3 groups(P<0.05).According to the size of the metabolic rate,it can be seen that CYP2D6*1(*2)/*14 belongs to slow metabolism type(PM),CYP2D6*1(*2)/*5 belongs to medium-speed metabolic type(IM),CYP2D6*10/*14 It belongs to fast metabolizing type(EM).Conclusion Different gene types of CYP2D6 can affect the metabolism of RIS and 9-OH-RIS,and then affect the plasma concentrations of RIS and 9-OH-RIS.CYP2D6 can be divided into three types according to different genotypes: PM,IM and EM.That is,PM patients have slower metabolism of RIS and 9-OH-RIS,and higher blood concentration,which may cause side effects;however,EM patients have faster metabolism of RIS and 9-OH-RIS,which may be needed for clinical treatment.A larger dose of RIS is treated.In summary,doctors can use RIS to treat schizophrenia patients in a planned manner according to their different genotypes,to alleviate unnecessary pain and increase patient compliance,from another perspective.Reduce doctor-patient disputes.