摘要
目的探讨CYP2D6的基因多态性对帕利哌酮血药浓度及临床疗效的影响,以及发现帕利哌酮在不同个体间代谢差异的遗传背景。方法选取66例符合诊断标准的精神分裂症患者为研究对象,患者正规服用抗精神病药帕利哌酮缓释片治疗4周。于清晨空腹抽取静脉血,在第2、4周末采用高效液相色谱法测定帕利哌酮的血药浓度,CYP2D6基因多态性由上海康黎医学检验所测定。结果 66例患者的CYP2D6基因多态性检测结果:C/C型为6例(9.1%),C/T型为41例(62.1%),T/T型为19例(28.8%)。经2周或4周治疗后,观察到C/C型患者的帕利哌酮血药浓度/剂量比最高,C/T型次之,最低为T/T型。在第4周末时,帕利哌酮的治疗有效率与第2周末相比明显增加(P<0.05),各基因型的治疗有效率由高到低的顺序分别为:C/C型、C/T型、T/T型。结论 CYP2D6基因多态性可影响帕利哌酮的血药浓度,但是否影响药物的临床疗效,还有待进一步探讨。
OBJECTIVE To investigate the potential influence of CYP2D6 gene polymorphisms on the blood concentration and therapeutic effects of paliperidone in schizophrenia,and to detect the genetic background of variations for paliperidone metabolism in different individuals. METHODS A total of 66 patients who met the diagnostic criteria of schizophrenia and took regularly paliperidone for 4 weeks were included. Steady serum concentration were monitored from venous blood drawed in the morning. High performance liquid chromatography (HPLC) was used to measure the serum concentration of paliperidone which was standardized by dosage. The genotypes of CYP2D6 in the subject were determined by Shanghai conlight medical. RESULTS There were 6 patients with C/C genotype(9.1%),41 patients with C/T(62.1%),and 19 patients with T/T(28.8%). After 2 or 4 weeks of treatment,the concentration/dose ratios could be influenced by genotype of CYP2D6. Ratios of C/C genotype patients was the highest,and those of T/T was the lowest. At the end of the fourth weekend,the effective rate of paliperidone increased significantly compared with that of the second weekend (P<0.05). The effective rates of genotypes ranged from high to low in the order of C/C,C/T and T/T. CONCLUSION For clinical efficacy,it seemed that the genotypes of CYP2D6 is associated with the blood concentration of paliperidone,but the effects on efficacy of paliperidone need to be further explored.
作者
高永双
平军娇
黄彩英
万静
薛坤喜
梁灵君
杜宝国
GAO Yongshuang;PING Junjiao;HUANG Caiying;WAN Jing;XUE Kunxi;LIANG lingjun;DU Baoguo(Zhongshan Third People's Hospital,Zhongshan ,Guangdong 528451,China)
出处
《今日药学》
CAS
2018年第12期829-831,838,共4页
Pharmacy Today
基金
广东省医学科学技术研究基金(A2018261)
