基于群体药动学模型的万古霉素个体化用药实践

Practiceof Individual Vancomycin Administration Based on Population Pharmacokinetic Model

目的:探讨万古霉素群体药动学(PPK)模型在临床的应用模式,与常规治疗药物监测(TDM)对比,分析PPK模型用于个体化给药的优势和可行性。方法:设计随机对照试验,制定严格的纳入和排除标准。共纳入65例患者,随机分为试验组34例和对照组31例。对照组患者进行常规TDM监测,试验组患者的经验性用药剂量根据PPK模型预测计算,以提高剂量合理性。比较两组患者首次万古霉素血药浓度达标率、临床疗效、细菌学疗效、药品不良反应等指标差异。结果:试验组患者首次万古霉素血药浓度(C1)达标率明显高于对照组(P<0.01),C1达标所需天数、万古霉素用药天数和住院天数均明显短于对照组(P<0.01或P<0.05)。两组细菌学疗效和临床有效率比较差异无统计学意义(P>0.05),试验组死亡率明显低于对照组(P<0.05)。两组药品不良反应发生率差异无统计学意义(P>0.05)。结论:PPK模型用于万古霉素个体化给药可显著提高谷浓度达标率,缩短万古霉素调整天数、万古霉素用药天数、ICU住院天数,并降低死亡率,可提高选用万古霉素经验性剂量的准确度,提高万古霉素用药剂量的合理性。

Objective:To discuss the clinical application mode of population pharmacokinetic(PPK)model of vancomycin and compare with the conventional TDM to analyze the feasibility and superiority of PPK model for vancomycin individual administration.Methods:A randomized controlled trial was conducted with strict inclusion and exclusion criteria.Totally 65 patients were involved.In the control group,the patients were given the conventional TDM.In the test group,the empirical dose of vancomycin was calculated by the PPK model to improve the rationality of administration dose.The collected data included demographics,physiology,pathology,therapy medicine and adverse drug reactions.At last,the differences in clinical efficacy,bacteriological efficacy and adverse drug reactions were evaluated between the groups.Results:Compared with that in the control group,the standard-obtained rate of the first vancomycin concentration(C1)was higher in the test group(P<0.01),and the dosage adjustment days were shorter in the test group(P<0.01).In the control group,the days of vancomycin administration and ICU stay were longer(P<0.05).The mortality rate of the control group was higher than that of the test group(P<0.005).Conclusion:Individual vancomycin administration based on the PPK model can shorten the days of vancomycin adjustment,vancomycin administration and ICU stay,reduce the mortality rate and increase the standard-obtained rate of concentration to improve the rationality of vancomycin dosage.