Alqurain Aymen Ali, Alrashidi Laila Nasser, Aloraifej Shatha Khalid, Alkhalifah Moayd, Alsayed Hawra Ali, Abohelaika Salah, Alshabeeb Mohammad A, Aldhafeeri Amal Shibak, Almuslim Moyad, Bumozah Thuraya Nasser, Alomar Mukhtar Jawad, Alshehab Azhar Abdullah, Alamer Ahmed AbdulWahab, Al-Matouq Jenan, Bidasee Keshore R, Alomar Fadhel A
Department of Clinical Practice, College of Pharmacy, Northern Border University, Rafha, 91911, Saudi Arabia.
Department of Pharmacy, Mohammed Al-Mana College for Medical Sciences, Dammam, 34222, Saudi Arabia.
Drug Des Devel Ther. 2024 Dec 21;18:6185-6198. doi: 10.2147/DDDT.S496512. eCollection 2024.
Vancomycin is commonly prescribed in treatment of methicillin-resistant Staphylococcus aureus infections. While, vancomycins' pharmacokinetic vary among older patients, there is a paucity of data regarding specific characteristics influencing pharmacokinetics in Saudi adult patients. This study aims to establish a population-pharmacokinetic (Pop-PK) model for vancomycin in patients admitted to medical wards, with the focus on identification of patient characteristics influencing vancomycin trough concentrations.
A multicenter retrospective study was conducted involving patients aged ≥40 years admitted to medical wards in the Eastern Province, Saudi Arabia and initiated on vancomycin, between January to December 2022. Non-linear mixed-effects modelling (Monolix) was employed to develop the Pop-PK model. A base model was selected based on the Akaike information criterion. Covariates considered included age, sex, body weight, C-reactive protein (CRP), serum creatinine, creatinine clearance (CrCl), and albumin levels. A -value of <0.05 was considered statistically significant for inclusion of covariates in the final model by stepwise addition. The simulation performance of the model was assessed by visual predictive check plot. The final model was simulated using Simulx software to assess the effect of the included covariates on vancomycin trough concentration.
A total of 172 vancomycin trough concentrations from 124 patients were analyzed. The final Pop-PK model characterized vancomycin trough concentrations was one compartment distribution with linear elimination. CrCl and CRP were the only covariates included in the final model, as they reduced the between-subject variability (BSV) for clearance (from 173% to 81%). The simulated model demonstrated that high CRP value and low CrCl contributed to increased vancomycin trough concentrations.
This study highlights large BSV in trough concentrations among patients and emphasizes the influencing of CrCl and CRP on vancomycin pharmacokinetics in medical care settings.
万古霉素常用于治疗耐甲氧西林金黄色葡萄球菌感染。然而，老年患者中万古霉素的药代动力学存在差异，关于影响沙特成年患者药代动力学的具体特征的数据却很匮乏。本研究旨在建立入住内科病房患者万古霉素的群体药代动力学（Pop-PK）模型，重点是识别影响万古霉素谷浓度的患者特征。
进行了一项多中心回顾性研究，纳入2022年1月至12月期间在沙特阿拉伯东部省份入住内科病房且开始使用万古霉素的年龄≥40岁的患者。采用非线性混合效应建模（Monolix）来建立Pop-PK模型。根据赤池信息准则选择基础模型。考虑的协变量包括年龄、性别、体重、C反应蛋白（CRP）、血清肌酐、肌酐清除率（CrCl）和白蛋白水平。通过逐步添加，将最终模型中纳入协变量的P值<0.05视为具有统计学意义。通过可视化预测检查图评估模型的模拟性能。使用Simulx软件对最终模型进行模拟，以评估纳入的协变量对万古霉素谷浓度的影响。
共分析了124例患者的172个万古霉素谷浓度。最终表征万古霉素谷浓度的Pop-PK模型为具有线性消除的一室分布。CrCl和CRP是最终模型中仅有的协变量,因为它们降低了清除率的个体间变异性（BSV）（从173%降至81%）。模拟模型表明，高CRP值和低CrCl会导致万古霉素谷浓度升高。
本研究突出了患者谷浓度中存在较大的个体间变异性，并强调了CrCl和CRP在内科护理环境中对万古霉素药代动力学的影响。
