目的 对肺移植术后1年影响他克莫司剂量和血药浓度的生理生化因素和遗传因素进行分析考察,为他克莫司的临床个体化用药提供参考。方法 选取2017年4月至2018年8月于我院行肺移植术的50例患者为研究对象,收集患者手术1年后基本信息,包括各项生理生化指标和他克莫司的用药剂量。采用化学发光微粒子免疫法测定他克莫司浓度,采用Sanger法测定患者细胞色素P450(CYP)3A5基因型。计算经体重校正的日剂量(D)和经剂量校正的血药浓度(C/D)值。分析CYP3A5基因型和生理生化指标对D和C/D的影响,运用多元线性回归确定D的影响因素。结果 在维持他克莫司浓度在治疗浓度范围内的条件下,CYP3A5*1/*1型和*1/*3型患者所需D高于*3/*3型患者,C/D值低于*3/*3型患者,差异有统计学意义(P<0.05)。多元线性回归结果显示,CYP3A5基因型、血红蛋白和年龄这3个变量对他克莫司D有显著影响,其中,血红蛋白和年龄与他克莫司D呈负相关(P<0.05)。运用多元线性回归预测公式计算得到D预测值,预测剂量与实际剂量之间的相关系数为0.824(95% CI:0.705~0.893)。结论 肺移植患者术后他克莫司剂量与CYP3A5基因型、血红蛋白和年龄具有相关性。运用上述指标预测他克莫司剂量可以为临床用药提供参考。
Abstract
OBJECTIVE To investigate the influence of patients' genetic and clinical parameters on tacrolimus dosage and concentration after lung transplantation. METHODS A total of 50 patients who had received lung transplantation in our hospital from April 2017 to August 2018 were enrolled in this study. Information was collected 1 year after transplantation. Tacrolimus concentration was determined by chemiluminescent microparticle immunoassay (CMIA) and CYP3A5 genotype was detected by Sanger sequencing. Body weight adjusted dosage (D) and dosage adjusted concentration (C/D) were calculated. Influence of CYP3A5 genotype on D and C/D were analyzed. Multiple linear regression was performed to determine influential factors on tacrolimus dosage 1 year after lung transplantation. RESULTS While maintaining tacrolimus concentration within therapeutic range, dosage requirement for CYP3A5*1/*1 and *1/*3 patients was higher than that of *3/*3 patients and C/D value was lower than that of *3/*3 patients (P<0.05). Multivariable linear regression results showed that CYP3A5 genotype, hemoglobin and age had significant influence on tacrolimus D, among which hemoglobin and age showed negative correlation (P<0.05). Prediction equation for tacrolimus D was obtained by multivariable linear regression. The correlation coefficient between predicted dose and actual dose was 0.824 (95% CI:0.705-0.893). CONCLUSION Tacrolimus dosage after lung transplantation is influenced by CYP3A5 genotype, hemoglobin and age. Using these factors for tacrolimus dosage prediction could possibly be instructive for individualized use of tacrolimus.
关键词
他克莫司 /
肺移植 /
CYP3A5 /
生理生化指标
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Key words
tacrolimus /
lung transplantation /
CYP3A5 /
clinical parameter
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中图分类号：
R969
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脚注
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基金
国家自然科学基金青年基金项目资助(81402942)
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