万古霉素群体药代动力学在肾功能亢进患者中的临床验证

Clinical verification of vancomycin population pharmacokinetics in patients with augmented renal clearance

目的 评价万古霉素群体药代动力学软件(JPKD-vancomycin)在肾功能亢进(ARC)患者中对万古霉素谷浓度的预测能力,并验证其临床应用效果,为临床个体化用药提供参考.方法 采用回顾性方法,收集2013年7月至2017年7月南京医科大学附属苏州医院收治的在住院期间使用万古霉素抗感染治疗并监测了稳态谷浓度的48例ARC患者的临床资料.采用经典药代动力学软件(Vancomycin Calculator)与JPKD-vancomycin软件相结合的方法,根据患者的性别、年龄、身高、体重、血肌酐(SCr)值及疾病状况,应用Vancomycin Calculator软件获得推荐给药方案及万古霉素稳态血药谷浓度,再应用JPKD-vancomycin软件预测初始方案的稳态血药谷浓度;若患者在治疗过程中调整了给药方案,则应用JPKD-vancomycin软件预测调整方案后的稳态血药谷浓度.记录万古霉素稳态血药谷浓度的实测值,并计算预测谷浓度与实测谷浓度之间的权重偏差(WRES),评估JPKD-vancomycin软件对万古霉素谷浓度的预测能力,以WRES<30%代表预测良好.结果 48例ARC患者均纳入最终分析,其中24例在治疗过程中调整了给药方案,最终共收集到谷浓度血样72份,包括初始谷浓度血样48份,调整用药方案后的谷浓度血样24份.初始给药方案及调整方案后的万古霉素应用剂量分别为(2000±500)mg/d和(2500±600)mg/d,稳态谷浓度分别为(8.4±7.3)mg/L和(9.1±4.3)mg/L.初始给药方案目标谷浓度10~20 mg/L的达标率仅14.6%,调整方案后达标率为25.0%,二者比较差异无统计学意义(P>0.05).用JPKD-vancomycin软件预测调整方案后的万古霉素谷浓度的WRES值明显低于初始方案谷浓度的WRES值〔10.6%(3.0%,16.4%)比14.3%(10.5%,38.2%),P<0.05〕,且WRES<30%的百分比亦呈升高趋势〔95.8%(23/24)比70.8%(34/48),P<0.05〕.JPKD-vancomycin软件对万古霉素谷浓度的预测良好率达79.2%(57/72),但有15例次WRES>30%.结论 JPKD-vancomycin软件对ARC患者万古霉素谷浓度的预测能力良好,尤其预测调整给药方案后的谷浓度更准确,能够为临床给药方案的设计提供支持.

Objective To evaluate the predictive value and to verify the clinical effect of JPKD-vancomycin for the trough concentration of vancomycin in patients with augmented renal clearance (ARC), and to provide a reference for clinical individualized drug therapy. Methods A retrospective analysis was conducted. The clinical data of 48 adult patients with ARC using vancomycin and monitoring steady-state trough concentration of vancomycin admitted to Suzhou Hospital Affiliated to Nanjing Medical University from July 2013 to July 2017 were collected. A combination of classical Vancomycin Calculator software and JPKD-vancomycin software was used. Based on the individual conditions of patients [gender, age, height, weight, serum creatinine (SCr), disease status], Vancomycin Calculator software was used to obtain the recommended regimen and its steady-state trough concentration, and then JPKD-vancomycin software was used to predict the steady-state trough concentration of initial regimen. If the regimen was adjusted during the treatment, JPKD-vancomycin software was used to predict the steady-state trough concentration of the adjusted regimen. The measured values of steady-state trough concentration were recorded. The weight deviation between predicted concentration and measured concentration (WRES) was calculated. WRES < 30% was considered as good prediction, and the predictive value of JPKD-vancomycin software was evaluated for vancomycin trough concentration. Results Forty-eight patients with ARC were enrolled, of whom 24 patients had adjusted the dosing regimen during the treatment. The initial concentration of blood samples was 48, after adjusting the dosage regimen, 24 blood samples were collected. The initial and adjusted daily dose of vancomycin was (2 000±500) mg/d and (2 500±600) mg/d, respectively, and the initial trough concentrations and adjusted trough concentrations was (8.4±7.3) mg/L and (9.1±4.3) mg/L, respectively. Only 14.6% and 25.0% of initial and adjusted trough concentrations reached the target range (10-20 mg/L) without significant difference (P > 0.05). The WRES value of adjusted trough concentrations predicted by JPKD-vancomycin software was significantly lower than that of initial regimen [10.6% (3.0%, 16.4%) vs. 14.3% (10.5%, 38.2%), P < 0.05], and the percentage of WRES < 30% also tended to increase (95.8% (23/24) vs. 70.8% (34/48), P < 0.05)The well predictive rate of JPKD-vancomycin software for vancomycin trough concentration was 79.2% (57/72), but there were 15 patients with WRES > 30%. Conclusions JPKD-vancomycin software has good predictive value for the vancomycin trough concentration of ARC patients, especially for the trough concentration after adjusting the treatment regimen. JPKD-vancomycin can provide a reference for the design of clinical individualized application of vancomycin.