CYP2D6联合CYP1A2基因多态性对老年晚期癌症伴发 抑郁状态患者奥氮平个体化用药的指导研究

目的：研究老年晚期癌症伴发抑郁状态患者细胞色素酶P450（Cytochrome P450，CYP）2D6联合CYP1A2基因多态性指导奥氮平（olanzapine，OLA）个体化用药。方法：选取2016年9月~2018年1月入院治疗的老年晚期癌症伴发抑郁状态患者80例，利用SPSS 23.0软件随机分为对照组20例和试验组60例，第1周对照组根据经验给予奥氮平初始剂量5 mg·d-1，试验组根据CYP2D6联合CYP1A2基因型给予不同初始剂量奥氮平（联合快代谢型为7.5 mg·d-1，中等代谢型为5 mg·d-1）。第2、3、4周根据奥氮平血药浓度、病情、不良反应调整剂量。给药后第1、4周末，比较两组血药浓度达标情况及疗效。结果：第1周末，试验组血药浓度、达到靶血药浓度范围患者比例、标准化血药浓度、HAMD-24减分率显著高于对照组（14.13±3.95） vs. （9.59±3.83） ng·L-1，86.7% vs. 60.0%，（38.90±15.51） vs.（30.93±13.55） ng·mL-1·mg-1·kg-1，（28.17±6.52）% vs.（23.27±5.45）%，P<0.05]，试验组4周调整剂量患者比例显著低于对照组（20.0% vs. 50.0%，P<0.05）。第1、4周末，试验组快代谢型与中等代谢型患者上述指标均无显著差异（P>0.05）。第1周末，试验组快代谢型患者血药浓度、达到靶血药浓度范围患者比例、标准化血药浓度、HAMD-24减分率显著高于对照组快代谢型（15.13±3.61） ng·L-1 vs. （6.27±2.62） ng·L-1，86.9% vs. 14.3%，（32.53±11.45） ng·mL-1·mg-1·kg-1 vs. （19.27±8.00） ng·mL-1·mg-1·kg-1，（28.49±5.96）% vs. （21.01±5.44）%，P<0.05]，试验组快代谢型4周调整剂量患者比例显著低于对照组快代谢型（17.4% vs. 100.0%，P<0.05）。结论：根据CYP2D6联合CYP1A2基因代谢型指导老年晚期癌症伴发抑郁状态患者服用奥氮平的初始剂量，能够更加有效地使各代谢型患者在治疗早期尽快达到有效奥氮平血药浓度。

Individualized Administration of Olanzapine Based on Gene Polymorphism of CYP2D6 and CYP1A2 in Elder Advanced Cancer Patients with Depression State

Objective: To investigate the guidance of gene polymorphism of CYP2D6 and CYP1A2 on individualized administration of olanzapine in elder advanced cancer patients with depression state. Methods: Eighty elder cancer patients with depression state from September 2016 to January 2018 were enrolled in this study. SPSS 23.0 was used to randomly divide the patients into control group (20 cases) and experimental group (60 cases). The patients in the control group were given initial dose of olanzipine at 5 mg·d-1 according to clinical experience, those in the experimental group were given different doses of olanzipine based on their genotype of CYP2D6 and CYP1A2 (7.5 mg·d-1 for extensive metabolizer, 5 mg·d-1 for intermediate metabolizer). The dosage of olanzaipine was adjusted according to the serum concentrations, patients'' conditions and adverse drug reactions. At the end of the 1st and 4th week after administration, the serum concentrations and clinical efficacy of the two groups were compared. Results: At the end of the 1st week, the serum concentrations, the proportion of patients reaching the target serum concentration range, standardized serum concentration and HAMD-24 reduction rate of the experimental group were significantly higher than those of the control group(14.13±3.95) vs.(9.59±3.83) ng·L-1, 86.7% vs. 60.0%, (38.90±15.51) vs. (30.93±13.55) ng·mL-1·mg-1·kg-1, (28.17±6.52)% vs. (23.27±5.45)%, P<0.05]. The proportion of patients with dose adjusted in 4 weeks in the experimental group was significantly lower than that in the control group (20.0% vs. 50.0%, P<0.05). At the end of the 1st and 4th week, there were no significant differences of the above indexes between the extensive metabolizers and the intermediate metabolizers in the experimental group (P>0.05). At the end of the 1st week, the serum concentrations, the proportion of patients reaching the target serum concentration range, standardized serum concentration and HAMD-24 reduction rate of the extensive metabolizers in the experimental group were significantly higher than those of the extensive metabolizers in the control group (15.13±3.61) vs. (6.27±2.62) ng·L-1, 86.9% vs. 14.3%, (32.53±11.45) vs. (19.27±8.00) ng·mL-1·mg-1·kg-1, (28.49±5.96)% vs.(21.01±5.44)%, P<0.05]. The proportion of patients with dose adjusted in 4 weeks of the extensive metabolizers in the experimental group was significantly lower than that of the extensive metabolizers in the control group(17.4% vs. 100.0%, P<0.05). Conclusions: Based on the gene polymorphism of CYP2D6 and CYP1A2, adjusting the initial dosage of olanzapine in elder advanced cancer patients with depression state can make patients with different metabolic genotype reach effective olanzapine serum concentration as soon as possible.