Shi Ying, He Juan, Mao Enqiang, Bian Xiaolan, Zhou Jiefang, Chen Erzhen
Department of Clinical Pharmacy, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing 312000, Zhejiang, China.
Department of Clinical Pharmacy, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020 Feb;32(2):140-144. doi: 10.3760/cma.j.cn121430-20190905-00026.
To observe the changing characteristics of pharmacokinetic and pharmacodynamic (PK-PD) parameters of vancomycin in critical patients under different drug regimens and to further explore the influencing factors.
The clinical data of patients who treated with vancomycin and recorded by steady-state through concentration (C) admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to December 2018 were analyzed retrospectively. The patients were divided into three groups according to the dosing interval (groups of q12 h, q8 h and q6 h respectively) and C was collected. The serum concentration of vancomycin before (0 hour) and 1, 2, 4, 6, 8, 12 and 24 hours after administration were estimated by JPKD Ver 3.1. Area under the curve (AUC) was estimated by trapezoidal area method. Minimum inhibitory concentration (MIC) of pathogenic microorganisms in the same period was retrieved, thus AUC/MIC was calculated.
285 patients with 529 records of Cmin were enrolled in the study, including 375 data in q12 h group, 121 data in q8 h group and 33 data in q6 h group. After unifying daily dose by JPKD Ver 3.1, the Cmin (10-20 mg/L) reaching rate of q12 h group, q8 h group, q6 h group were 35.7%, 43.8% and 60.6%, respectively, while only q12 h group was statistically significant compared with q6 h group (P < 0.01). q6 h group and q8 h group showed higher Cmin than q12 h group (mg/L: 13.8±5.2, 13.5±7.3 vs. 11.4±7.9, both P < 0.05) and lower peak concentration (C) than q12 h group (mg/L: 19.4±5.3, 21.5±7.3 vs. 23.9±8.1, both P < 0.05). However, there was no significant difference in terms of percentage of PD target (AUC/MIC ≥ 400) among the three groups (q12 h group, q8 h group, q6 h group were 38.1%, 41.3%, 45.5%, P > 0.05). Multiple linear regression analysis showed that creatinine clearance (CCr) and vancomycin clearance (CL) were the main influencing factors of vancomycin PD parameters such as Cmin and AUC/MIC (r values of CCr were -0.391, -0.424, and rvalues of CL were -0.673, -0.663, all P < 0.01), and were negatively correlated with age (r values were -0.432 and -0.488, respectively, both P < 0.01).
At the same daily dose, C can be increased and C can be decreased by increasing the frequency of vancomycin administration, thus minimize the fluctuation of vancomycin serum concentration, but AUC/MIC is not affected. Vancomycin administration regimen in severe patients should be optimized according to CCr, CL and age.
观察不同给药方案下重症患者万古霉素药代动力学和药效学（PK-PD）参数的变化特征，并进一步探讨其影响因素。
回顾性分析2011年1月至2018年12月在上海交通大学医学院附属瑞金医院重症监护病房（ICU）接受万古霉素治疗并记录稳态谷浓度（C）的患者临床资料。根据给药间隔将患者分为三组（分别为q12 h组、q8 h组和q6 h组）并采集C。采用JPKD Ver 3.1估算给药前（0小时）及给药后1、2、4、6、8、12和24小时的万古霉素血清浓度。采用梯形面积法估算曲线下面积（AUC）。检索同期致病微生物的最低抑菌浓度（MIC），进而计算AUC/MIC。
本研究纳入285例患者共529条Cmin记录，其中q12 h组375条数据，q8 h组121条数据，q6 h组33条数据。经JPKD Ver 3.1统一每日剂量后，q12 h组、q8 h组、q6 h组的Cmin（10 - 20 mg/L）达标率分别为35.7%、43.8%和60.6%；仅q12 h组与q6 h组比较差异有统计学意义（P < 0.01）。q6 h组和q8 h组的Cmin高于q12 h组（mg/L：13.8±5.2，13.5±7.3比11.4±7.9，均P < 0.05），峰浓度（C）低于q12 h组（mg/L：19.4±5.3，21.5±7.3比23.9±8.1，均P < 0.05）。然而，三组间PD目标（AUC/MIC≥400）百分比差异无统计学意义（q12 h组、q8 h组、q6 h组分别为38.1%、41.3%、45.5%，P > 0.05）。多元线性回归分析显示，肌酐清除率（CCr）和万古霉素清除率（CL）是万古霉素PD参数如Cmin和AUC/MIC的主要影响因素（CCr的r值分别为-0.391、-0.424，CL的r值分别为-0.673、-0.663，均P < 0.01），且与年龄呈负相关（r值分别为-0.432和-0.488，均P < 0.01）。
在每日剂量相同的情况下，增加万古霉素给药频率可使Cmin升高、Cmax降低，从而使万古霉素血清浓度波动最小化，但不影响AUC/MIC。重症患者万古霉素给药方案应根据CCr、CL及年龄进行优化。
