Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Clinical Pharmacokinetics and Pharmacodynamics Unit, King Saud University Medical City, Riyadh, Saudi Arabia.
Pharmacotherapy. 2020 Dec;40(12):1192-1200. doi: 10.1002/phar.2475. Epub 2020 Nov 23.
Gram-positive bacterial infections are considered one of the major causes of mortality and morbidity in patients with cancer. Hence, the challenge lies in regulating the pervasive use of vancomycin in the management of infections facing such patients due to the anomalous vancomycin pharmacokinetics (PKs) and pharmacodynamics (PDs). Inappropriate vancomycin exposure is associated with toxicity, pathogen resistance, and therapeutic failure.
The aim of this study was to estimate vancomycin PK in patients with cancer and without cancer. The standard dosage regimens of vancomycin were then evaluated using data from PK modeling.
In this observational PK study, the data were extracted from a matched patient cohort of those with cancer and those without cancer. Pharmacokinetic analysis was performed using Monolix version 4.4, and the PK parameters were compared in both groups (cancer vs noncancer). The standard and suggested vancomycin dosing regimens were evaluated using PK/PD modeling and Monte Carlo Simulations.
In total, 448 blood samples were analyzed from 147 patients enrolled in this study, of which 73 patients had cancer and 74 patients were noncancer patients. In general, no significant differences were observed between the two groups (cancer vs noncancer) in all characteristics except for the vancomycin levels, which were significantly lower in patients with cancer (p = 0.00104). This analysis showed that patients with cancer showed a significantly higher vancomycin clearance than noncancer patients (p = 0.002), whereas the volume of distribution (V) was found to be similar in both groups (p = 0.83).This resulted in most of the patients failing to achieve the target area under the curve from zero to 24 hours (AUC ) to the minimum inhibitory concentration. These data showed that a higher maintenance dose of vancomycin is required to achieve the PD target.
The findings of this study showed that the patients with cancer have lower levels of vancomycin due to higher clearance than noncancer patients. Thus, higher doses than the standard vancomycin doses may be needed to treat invasive Methicillin-resistant Staphylococcus aureus infections in patients with cancer.
革兰氏阳性菌感染被认为是癌症患者死亡和发病的主要原因之一。因此，由于异常的万古霉素药代动力学（PK）和药效动力学（PD），在管理此类患者面临的感染时，如何规范万古霉素的广泛使用是一个挑战。不适当的万古霉素暴露与毒性、病原体耐药性和治疗失败有关。
本研究旨在评估癌症患者和非癌症患者的万古霉素 PK。然后使用 PK 建模数据评估标准万古霉素剂量方案。
在这项观察性 PK 研究中，从癌症患者和非癌症患者的匹配患者队列中提取数据。使用 Monolix 版本 4.4 进行 PK 分析，并比较两组（癌症与非癌症）的 PK 参数。使用 PK/PD 建模和蒙特卡罗模拟评估标准和建议的万古霉素剂量方案。
本研究共分析了 147 名入组患者的 448 份血样，其中 73 名患者患有癌症，74 名患者为非癌症患者。一般来说，除了万古霉素水平外，两组之间（癌症与非癌症）在所有特征上均无显著差异，而癌症患者的万古霉素水平明显较低（p=0.00104）。这项分析表明，癌症患者的万古霉素清除率明显高于非癌症患者（p=0.002），而两组之间的分布容积（V）相似（p=0.83）。这导致大多数患者未能达到 0 至 24 小时的目标 AUC 至最低抑菌浓度。这些数据表明，需要更高的万古霉素维持剂量才能达到 PD 目标。
本研究结果表明，由于清除率较高，癌症患者的万古霉素水平较低。因此，癌症患者可能需要比标准万古霉素剂量更高的剂量来治疗侵袭性耐甲氧西林金黄色葡萄球菌感染。
