某三甲精神病院利培酮血药浓度监测现状及影响因素分析

Serum concentration monitoring and influential factors analysis of risperidone in a grade A psychological hospital

目的:通过分析某三甲精神病院利培酮(risperidone,RIS)血药浓度监测(therapeutic drug monitoring,TDM)现状,探索RIS血药浓度影响因素。方法:采用回顾性分析方法,收集2019年7月至2020年7月进行RIS TDM住院患者的检测结果及相关病例资料,分析利培酮、活性代谢物9-羟基利培酮(9-OH-RIS)以及总活性成分(active moiety,AM)血药浓度值的分布情况,探索日剂量、性别、年龄对血药浓度的影响以及体质量和体质指数(body mass index,BMI)与血药浓度的相关性。结果:1007例患者共行RIS TDM 4458例次,平均监测次数为4.47次,29.99%例次监测结果不在建议的参考范围(20~60 ng·mL^(-1))内,临床实际RIS血药浓度值(C_(RIS))、9-OH-RIS血药浓度值(C_(9-OH-RIS))以及AM血药浓度值(C_(AM))的参考值范围分别为(0.45~39.79)、(8.43~74.87)和(11.74~97.23)ng·mL^(-1)。C_(AM)与日剂量具有相关性(ρ=0.536,P<0.01),C_(9-OH-RIS)与日剂量具有相关性(ρ=0.570,P<0.01),C_(RIS)与日剂量呈较弱的相关性(ρ=0.192,P<0.01)。女性较男性有更高的C_(AM)与AM浓度剂量比(C/D)值,不同年龄段患者C_(AM)与C/D值存在差异。体质量与C_(AM)(ρ=-0.065,P<0.01)和C/D值(ρ=-0.098,P<0.01)呈负相关,与RIS/9-OH-RIS比值(ρ=0.037,P=0.014)呈正相关。BMI与C_(AM)(ρ=-0.054,P<0.01)和C/D值(ρ=-0.033,P=0.026)呈负相关。结论:临床实际C_(AM)参考值范围相比于AGNP-TDM专家组推荐的参考范围更宽;日剂量、性别、年龄、体质量和BMI是影响C_(AM)以及C/D值的重要因素,这些因素或可以为RIS临床个体化用药提供参考。

OBJECTIVE To explore the relevant influencing factors of risperidone(RIS)concentration by analyzing the status of RIS therapeutic drug monitoring(TDM)at a class 3A psychological hospital.METHODS The monitoring results and relative data of patients were collected retrospectively from July 2019 to July 2020.Distribution of RIS concentration(C_(RIS)),active metabolite 9-hydroxyrisperidone(9-OH-RIS)concentration(C_(9-OH-RIS))and active moiety(sum of RIS+9-OH-RIS)concentration(C_(AM))were analyzed.The effects of daily dose,gender and age on concentration,as well as the correlations between body weight,body mass index(BMI)and concentration were examined individually.RESULTS All of 4458 samples were detected in 1007 patients with an average monitoring frequency of 4.47 times.However,around 29.99%of the results were beyond the recommended reference range(20-60 ng·mL^(-1)).In clinical practices,the corresponding reference values of C_(RIS),C_(9-OH-RIS) and C_(AM) were(0.45-39.79),(8.43-74.87)and(11.74-97.23)ng·mL^(-1) respectively.C_(AM) was correlated with daily dose(ρ=0.536,P<0.01)and C_(9-OH-RIS) correlated with daily dose(ρ=0.570,P<0.01).However,C_(RIS) was slightly correlated with daily dose(ρ=0.192,P<0.01).C_(AM) and dose-adjusted serum concentrations(C/D)of female were higher than those of male while significant differences existed in C_(AM) and C/D among patients with different ages.Body weight was correlated negatively with C_(AM)(ρ=-0.065,P<0.01)and C/D(ρ=-0.098,P<0.01)but positively with RIS/9-OH-RIS(ρ=0.037,P=0.014).Meanwhile,BMI was negatively correlated with C_(AM)(ρ=-0.054,P<0.01)and C/D(ρ=-0.033,P=0.026).CONCLUSION As compared with the reference range recommended by AGNP-TDM guideline,the clinical reference range of actual C_(AM) is wider.Both C_(AM) and C/D are affected by daily dose,gender,age,body weight and BMI.It may provide references for clinical individualized medication of RIS.