目的 明确亚甲基四氢叶酸还原酶（MTHFR）C677T、A1298C基因多态性与成人患者使用大剂量甲氨蝶呤（MTX）治疗急性淋巴细胞白血病（ALL）毒性反应和24、48、72 h MTX血药浓度关系。方法 收集2014年6月—2020年6月就诊于新疆医科大学第一附属医院成人急性淋巴细胞白血病75例患者血样检测MTHFR C677T及A1298C基因多态性, 根据抗癌药物常见毒性反应分级标准对毒性反应进行分级,采用非条件Logistic回归分析MTHFR C677T、A1298C基因多态性与HD-MTX毒性反应及血药浓度的关系。结果 MTHFR 677TT型发生贫血风险显著高于CC型（P=0.027, OR=4.694, 95%CI：1.195~18.438）; 未发现MTHFR C677T与白细胞减少、血小板计数减少、中性粒细胞计数减少、淋巴粒细胞计数减少、骨髓抑制、谷丙转氨酶升高、谷草转氨酶升高、肝功能损伤、急性肾损伤及黏膜损伤、24 h、48 h及72 h MTX血药浓度有相关性（P>0.05）; 未发现MTHFR A1298C与HD-MTX毒性反应及血药浓度有相关性（P>0.05）。结论 MTHFR C677T基因多态性与成人急性淋巴细胞白血病患者大剂量MTX化学治疗后血液毒性存在相关性。

Objective To determine the relationship among C677T and A1298C gene polymorphisms of methyltetrahydrofolate reductase（MTHFR）and adult acute lymphocytic leukemia（ALL）, the relationship between the toxicity of high-dose methotrexate（HD-MTX）after chemotherapy and the MTX blood concentration of 24 h, 48 h and 72 h in patients with ALL．Methods Blood samples were collected from 75 adult patients with ALL who were treated at the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2020．The samples were used to detect the genetic polymorphisms of MTHFR C677T and A1298C, and the toxic reactions were graded according to the common toxic reaction classification criteria of anti-cancer drugs．Unconditional Logistic regression was used to analyze the relationship between MTHFR C677T and A1298C gene polymorphisms and HD-MTX toxic reactions and blood drug concentration．Results The risk of anemia in MTHFR 677TT was significantly higher than that in CC type（P=0.027, OR=4.694, 95% CI：1.195-18.438）．No correlation was found between MTHFR C677T and leukopenia, thrombocytopenia, neutropenia, lymphogranulocytopenia, bone marrow suppression, elevated alanine aminotransferase, elevated aspartate aminotransferase, liver function injury, acute kidney injury and mucosal injury, 24 h, 48 h and 72 h MTX plasma concentrations（>0.05）．No correlation was found among MTHFR A1298C and HD-MTX toxicity and blood concentration（P>0.05）．Conclusions MTHFR C677T gene polymorphism is associated with hematotoxicity after HD-MTX chemotherapy in adult patients with ALL．

目的 探讨性别、年龄、日剂量、合并用药、药物厂家等因素对使用阿立哌唑患者稳态血药浓度的影响,为临床合理用药提供依据。方法 收集深圳市康宁医院2019年1月—2021年2月使用阿立哌唑住院患者血药浓度监测数据样本229份,包括患者性别、年龄、日剂量、合并用药、药物厂家等基本信息,使用SPSS 25.0统计学软件对数据进行回顾性分析。结果 经多元线性回归分析,本研究仅性别、日剂量能解释阿立哌唑血药浓度的变化。使用阿立哌唑患者血药浓度剂量比值(C/D)女性组高于男性组(P＜0.01),阿立哌唑合用丙戊酸盐组高于无合用组(P＜0.05),年龄、其他合并、药物厂家用药对阿立哌唑(C/D)值的影响无统计学差异。结论 阿立哌唑C/D值与性别有关,合并用药对其有一定影响,不同药物厂家的阿立哌唑C/D值无统计学差异,临床应加强治疗药物监测,根据血药浓度及临床诊疗效果,结合药物经济学因素优化给药方案。

Objective To provide the reference for clinical rational use of aripiprazole,to investigate the effects of gender, age, daily dose, concurrent medication, drug manufacturer and other factors on the steady-state serum concentration in aripiprazole patients. Methods Serum concentration monitoring data of 229 inpatients using aripiprazole in Shenzhen Kangning Hospital from January 2019 to February 2021 was collected, including patients' gender, age, daily dose, concurrent medication, drug manufacturer and other basic information, which were retrospectively analyzed by SPSS 25.0 statistical software. Results In this study, only gender and daily dose could explain the significant changes of aripiprazole serum concentration after multiple linear regression analysis. The serum concentration/dose ratio (C/D) was significantly higher in female patients than in male patients (P＜0.01), and the group of aripiprazole combined with valproate was markedly higher than the non-combined group (P＜0.05). Nevertheless, there were no statistically significant differences in the effects of age, concurrent medication and drug manufacturer on aripiprazole C/D values. Conclusions The C/D value of aripiprazole was closely related to gender, and concurrent medication had a certain effect on it. There was no statistical difference in the aripiprazole C/D value among different drug manufacturers. This study suggested that clinical monitoring of therapeutic drugs should be strengthened, and the prescription should be optimized based on serum concentration and therapeutic efficacy, combined with pharmacoeconomic factors.