Gan Yuhong, Meng Xiaobin, Lei Nanfeng, Yu Hong, Zeng Qingkao, Huang Qingyan
Department of Clinical Pharmacy, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, People's Republic of China.
Department of Intensive Care Unit, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, People's Republic of China.
Infect Drug Resist. 2023 Jun 21;16:3989-3997. doi: 10.2147/IDR.S408572. eCollection 2023.
This study aimed to investigate the pharmacokinetics and target attainment of meropenem and compare the effect of meropenem dosing regimens in critically ill patients.
Thirty-seven critically ill patients who were administered meropenem in intensive care units were analyzed. Patients were classified according to their renal function. Pharmacokinetic parameters were assessed based on Bayesian estimation. The target attainment of 40%fT > MIC (fraction time that the free concentration exceeds the minimum inhibitory concentration) and 100%fT > MIC with the pathogen MIC of 2 mg/L and 8 mg/L were specially focused. Furthermore, the effects of standard dosing (1g meropenem, 30 min intravenous infusion every 8h) and non-standard dosing (dosage regimens except standard dosing) were compared.
The results showed that the values of meropenem clearance (CL), central volume of distribution (V1), intercompartmental clearance (Q), and peripheral volume of distribution (V2) were 3.3 L/h, 9.2 L, 20.1 L/h and 12.8 L, respectively. The CL of the patients among renal function groups was significantly different ( < 0.001). The tow targets attainment for the pathogen MIC of 2 mg/L and 8 mg/L were 89%, 73%, 49% and 27%, respectively. The severe renal impairment group has higher fraction of target attainment than the other group. The standard dosing achieved the target of 40%fT > 2/8 mg/L (85.7% and 81%, respectively) and patients with severe renal impairment achieved the target fraction of 100% for 40%fT > MIC. Additionally, there was no significant difference between standard and non-standard dosing group in target attainment.
Our findings indicate that renal function is an important covariate for both meropenem pharmacokinetics parameters and target attainment. The target attainment between standard and non-standard dosing group was not comparable. Therefore, therapeutic drug monitoring is indispensable in the dosing adjustment for critically ill patients if it is available.
本研究旨在探讨美罗培南的药代动力学和达标情况，并比较美罗培南给药方案对重症患者的影响。
分析了37例在重症监护病房接受美罗培南治疗的重症患者。根据肾功能对患者进行分类。基于贝叶斯估计评估药代动力学参数。特别关注了病原体最低抑菌浓度（MIC）为2mg/L和8mg/L时，40%fT>MIC（游离浓度超过最低抑菌浓度的时间分数）和100%fT>MIC的达标情况。此外，比较了标准给药方案（1g美罗培南，每8小时静脉输注30分钟）和非标准给药方案（除标准给药方案外的其他给药方案）的效果。
结果显示，美罗培南清除率（CL）、中央分布容积（V1）、室间清除率（Q）和外周分布容积（V2）的值分别为3.3L/h、9.2L、20.1L/h和12.8L。肾功能组间患者的CL有显著差异（<0.001）。病原体MIC为2mg/L和8mg/L时，两个靶点的达标率分别为89%、73%、49%和27%。重度肾功能损害组的达标率高于其他组。标准给药方案达到了40%fT>2/8mg/L的目标（分别为85.7%和81%），重度肾功能损害患者达到了40%fT>MIC时100%的目标达标率。此外，标准给药组和非标准给药组在达标情况上无显著差异。
我们的研究结果表明，肾功能是美罗培南药代动力学参数和达标情况的重要协变量。标准给药组和非标准给药组的达标情况不可比。因此，在有条件的情况下，治疗药物监测对于重症患者的剂量调整是必不可少的。
