Department of Clinical Pharmacy, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Eur J Clin Pharmacol. 2021 Jun;77(6):831-840. doi: 10.1007/s00228-020-03062-0. Epub 2021 Jan 6.
No study has been evaluated pharmacokinetic (PK) and pharmacodynamic (PD) properties of β-lactam antibiotics in patients with acute kidney injury (AKI), not requiring renal replacement therapy (RRT). We evaluated the time that plasma concentrations remain above four times the MIC (ft > 4MIC) and PK parameters of meropenem in this population.
In this prospective, randomized clinical trial (RCT), all patients received standard dose (3 g daily) of meropenem for 48 h, then randomly allocated in standard or adjusted groups. The standard group received meropenem without dose adjustment. In the adjusted group, the meropenem dose was adjusted based on the Cockcroft-Gault(C-G) equation. Meropenem concentrations were measured at the peak and trough times on the 2nd and 5th days of the study.
On the 2nd day of the study, 3 out of 10 (30%) of patients attained the PD target (≥ 80%ft > 4MIC). In the 5th day of the study, the PD target was attained in 2 out of 10 (20%) and 1 out of 5 (20%) of patients who received standard and adjusted doses of meropenem, respectively (p = 1). In all samples, increased volume of distribution (Vd) (median; IQR) (46.04; 23.06-103.18 L), terminal half-life (T1/2) (4.51; 2.67-8.88 h) and decreased clearance (6.52; 4.43-10.16 L/h) have been shown.
In critically ill patients with AKI, who not receive RRT, standard doses, and adjusted according to renal function of meropenem failed to achieve PD target of ≥ 80%ft > 4MIC. Higher doses are required for this target.
The study protocol with registered retrospectively and approved on January 19, 2019, with the number of IRCT20160412027346N5.
目前尚无研究评估过无需肾脏替代治疗（RRT）的急性肾损伤（AKI）患者的β-内酰胺类抗生素的药代动力学（PK）和药效动力学（PD）特性。我们评估了该人群中美罗培南的血药浓度超过 4 倍 MIC（ft > 4MIC）的时间和 PK 参数。
在这项前瞻性、随机临床试验（RCT）中，所有患者接受标准剂量（每日 3 g）美罗培南治疗 48 小时，然后随机分为标准剂量组或调整剂量组。标准剂量组不调整美罗培南剂量。在调整剂量组中，根据 Cockcroft-Gault（C-G）方程调整美罗培南剂量。在研究的第 2 天和第 5 天，在峰时和谷时测量美罗培南浓度。
在研究的第 2 天，10 名患者中有 3 名（30%）达到了 PD 目标（≥ 80%ft > 4MIC）。在研究的第 5 天，标准剂量组和调整剂量组分别有 2 名（20%）和 1 名（20%）患者达到 PD 目标（p = 1）。在所有样本中，均显示分布容积（Vd）增加（中位数；IQR）（46.04；23.06-103.18 L）、半衰期（T1/2）延长（4.51；2.67-8.88 h）和清除率降低（6.52；4.43-10.16 L/h）。
在无需接受 RRT 的 AKI 危重症患者中，标准剂量和根据肾功能调整的美罗培南剂量均未能达到≥ 80%ft > 4MIC 的 PD 目标。需要更高的剂量才能达到这一目标。
该研究方案于 2019 年 1 月 19 日进行了回顾性注册，并获得批准，注册号为 IRCT20160412027346N5。
