CYP2D6基因多态性对阿立哌唑血药浓度及临床疗效的影响

Influence of CYP2D6 Gene Polymorphisms on the Blood Concentration of Aripiprazole and Therapeutic Efficacies

目的:探讨细胞色素P450酶亚型CYP2D6的基因多态性对阿立哌唑血药浓度及临床疗效的影响,以期为抗精神病药物个体化给药提供依据。方法:84例符合诊断标准的精神分裂症患者接受阿立哌唑为期4周的治疗,应用聚合酶链反应-限制性片断长度多态性方法(PCR-RFLP)检测84例患者CYP2D6 exonⅠC/T188位点的基因多态性;采用反相高效液相色谱法测定阿立哌唑的谷血药浓度;并在治疗第0、2、4周分别进行阳性和阴性综合征量表(PANSS)评分。结果:在84例患者中,C/C型7例(8.3%),C/T型43例(51.2%),T/T型34例(40.5%)。CYP2D6 exonⅠC/T188位点基因型可影响血药浓度/剂量比,C/C型血药浓度/剂量比最高,C/T型次之,T/T型最低。3种不同的基因型中,第2周末阿立哌唑的疗效差异无统计学意义,而第4周末时阿立哌唑疗效差异有统计学意义(P<0.05)。结论:CYP2D6 exonⅠC/T188基因多态性可影响阿立哌唑的血药浓度及临床疗效。对于T/T型患者采用阿立哌唑治疗时可以加大起始剂量,若加大起始剂量仍不能达到有效治疗浓度应考虑改用其他治疗方案;C/C型患者应给予相对较小的起始剂量就能达到治疗浓度,减少由于血药浓度过高导致的药物毒性及不良反应。

OBJECTIVE： To explore the influence of cytochrome P450 CYP2D6 gene polymorphisms on the blood concentration and therapeutic efficacies of aripiprazole, and to provide reference for individual administration of antipsychotic drug. METHODS ： 84 schizophrenia patients received treatment of aripiprazole for 4 weeks. The gene polymorphism of CYP2D6 exon I C/T188 in 84 patients were detected with PCR-RFLE Trough concentration of aripiprazole was measured by RP-HPLC; and the therapeutic effica- eies were evaluated with PANSS after 0, 2 and 4 weeks. RESULTS： Among 84 patients, there were 7 patients with C/C genotype （8.3%）, 43 patients with C/T （51.2%）, and 34 patients with T/T （40.5%）. Blood concentration-dose ratios could be influenced by genotype of CYP2D6 exon [ C/T188. The blood concentration-dose ratio of C/C genotype was the highest, those of T/T were the lowest and those of C/T were moderate. There was no significant difference in therapeutic efficacies among 3 genotypes after the treatment of aripiprazole for 2 weeks, but statistical signiflcances were detected at 4th week （P^0.05）. CONCLUSIONS： The gene polymorphisms of CYP2D6 exon I C/T188 may be associated with both blood concentration of aripiprazole and therapeutic efficacies. Patients with TIT genotype might choose higher initial dose; therapeutic regimen should be changed if efficaciesive concen- tration could not be reached even at higher initial dose. Patients with C/C genotype might choose lower initial dose, so as to reduce drug toxicity and adverse drug reaction owing to too much high concentration.