Fu Wen-Qian, Tian Ting-Ting, Zhang Min-Xin, Song Hong-Tao, Zhang Li-Li
Department of Pharmacy, 900th Hospital of Joint Logistics Support Force, Fuzhou, China.
Department of Purchasing Management, 900th Hospital of Joint Logistics Support Force, Fuzhou, China.
Front Pharmacol. 2022 Nov 23;13:1045895. doi: 10.3389/fphar.2022.1045895. eCollection 2022.
To develop a population pharmacokinetic (PopPK) model describing unbound teicoplanin concentrations in Chinese adult patients and perform Monte Carlo simulations to optimize the dosing regimens. The raw data for PopPK analysis in this study were collected from Chinese adult patients. A PopPK model of unbound teicoplanin was developed and Monte Carlo simulations were used to optimize the dosing regimens. The trough concentrations of unbound teicoplanin were targeted at 0.75 mg/L and 1.13 mg/L for most infection induced by Gram-positive bacteria and endocarditis or severe infections, respectively. A total of 103 teicoplanin unbound concentrations were collected from 72 Chinese adult patients. A one-compartment pharmacokinetic model with first-order elimination was established. The typical values of clearance and the volume of distribution were 11.7 L/h and 811 L, respectively. The clearance and volume of distribution of unbound teicoplanin were positively correlated with estimated glomerular filtration rate (eGFR) and serum albumin concentrations, respectively. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and the dosing regimen need optimize based on eGFR and serum albumin concentrations. The high eGFR and serum albumin concentration were associated with reduced probability of achieving target unbound trough concentrations. We successfully characterized the pharmacokinetics of unbound teicoplanin in Chinese adult patients. Importantly, we further highlight the importance of guiding dosing through unbound drugs. To achieve safe and effective treatment, the dosing regimens need to be adjusted according to eGFR and serum albumin concentrations.
建立一个描述中国成年患者未结合替考拉宁浓度的群体药代动力学（PopPK）模型，并进行蒙特卡洛模拟以优化给药方案。本研究中PopPK分析的原始数据收集自中国成年患者。建立了未结合替考拉宁的PopPK模型，并使用蒙特卡洛模拟来优化给药方案。对于大多数革兰氏阳性菌引起的感染以及心内膜炎或严重感染，未结合替考拉宁的谷浓度目标分别为0.75mg/L和1.13mg/L。从72名中国成年患者中总共收集了103个未结合替考拉宁的浓度。建立了一个具有一级消除的单室药代动力学模型。清除率和分布容积的典型值分别为11.7L/h和811L。未结合替考拉宁的清除率和分布容积分别与估计肾小球滤过率（eGFR）和血清白蛋白浓度呈正相关。给药模拟结果表明，标准给药方案无法满足所有患者的治疗需求，给药方案需要根据eGFR和血清白蛋白浓度进行优化。高eGFR和血清白蛋白浓度与达到目标未结合谷浓度的概率降低相关。我们成功地描述了中国成年患者未结合替考拉宁的药代动力学。重要的是，我们进一步强调了通过未结合药物指导给药的重要性。为了实现安全有效的治疗，给药方案需要根据eGFR和血清白蛋白浓度进行调整。
