个体化给药辅助系统JPKD预测肾移植患者他克莫司血药浓度的准确性评估及影响因素分析

Evaluation of the Accuracy and Analysis of the Influencing Factors of Individualized Dosage Auxiliary System JPKD in Prediction of Tacrolimus Blood Concentration in Patients After Renal Transplantation

关键词:  他克莫司  个体化给药  JPKD  血药浓度  预测

Key words:  tacrolimus  individual drug therapy  JPKD  blood concentration  prediction

摘要:

目的 评估个体化给药辅助决策系统Java PK^® for Desktop(JPKD)在肾移植患者中预测他克莫司血药浓度的准确性，并分析预测准确性的影响因素。方法 采用回顾性调查分析方法，收集南京大学医学院附属金陵医院2019年9月—2020年1月肾移植术后使用他克莫司抗排斥治疗的病例，使用JPKD预测他克莫司剂量调整后的血药谷浓度，计算实测浓度与预测浓度之间的绝对权重偏差和相对预测误差，评估JPKD的预测能力。采用单因素和多因素Logistic回归分析筛选JPKD预测准确性的影响因素。结果 共收集31例患者101例次血药浓度数据，他克莫司血药浓度平均预测值为(6.91±2.65)μg·L^-1 (2.39~15.18 μg·L^-1)，平均实测值为(8.99±4.13)μg·L^-1(2.70~22.00μg·L^-1)，平均绝对权重偏差为28.46%，平均相对预测误差为-15.87%。预测值的绝对权重偏差<30%的占57.14%。单因素分析显示性别、身高、红细胞比容、CYP3A5基因型、合并使用泊沙康唑与预测结果不准确有关。多因素Logistic回归分析显示CYP3A5基因型、合并使用泊沙康唑是预测不准确的主要危险因素。结论JPKD系统对他克莫司的血药浓度具有一定的预测能力，在临床应用时需与CYP3A5基因型和合并用药相结合来制定个体化给药方案。

Abstract:

OBJECTIVE To investigate the accuracy of Java PK^® for Desktop(JPKD) in predicting the blood concentrations of tacrolimus in patients after renal transplantation and to analyze the factors affecting the accuracy of the prediction. METHODS A retrospective analysis method was used. Data of patients using tacrolimus to anti-rejection therapy after renal transplantation from September 2019 to January 2020 in Jinling Hospital, Nanjing University School of Medicine were collected. The absolute weight deviation and relative prediction error between the measured concentration and the predicted concentration were calculated by using JPKD to predict tacrolimus dose-adjusted plasma grain concentration, and the prediction ability of JPKD was evaluated. The univariate and multivariate Logistic regression analysis were used to screen the influence factors of JPKD prediction accuracy. RESULTS A total of 101 patients’ blood concentration data were collected from 31 patients. The average predicted concentration of tacrolimus was (6.91±2.65)μg·L^-1 (2.39-15.18 μg·L^-1), and the average measured concentration was (8.99±4.13)μg·L^-1 (2.70-22.00 μg·L^-1), with an average absolute weight deviation of 28.46% and an average relative prediction error of -15.87%. The absolute weight deviation of prediction results <30% accounts for 57.14%. Univariate Logistics regression analysis showed that gender, height, hematocrit, CYP3A5 genotype, and the combined use of posaconazole were associated with inaccurate prediction results. Multivariate Logistics regression analysis showed that the CYP3A5 genotype and the combined use of posaconazole were the main risk factors for inaccurate prediction. CONCLUSION JPKD system has a certain predictive ability for blood concentration of tacrolimus. In clinical application, it is necessary to combine JPKD system with the CYP3A5 genotype and the combined medication to develop an individualized drug therapy plan.