Faculty of Pharmacy, Université de Montréal, Pavillon Jean-Coutu, 2940 chemin de polytechnique, Montreal, QC, H3T 1J4, Canada.
Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada.
Clin Pharmacokinet. 2021 Apr;60(4):447-470. doi: 10.1007/s40262-020-00970-3. Epub 2021 Jan 15.
Lower respiratory tract infections are common in adult patients with cystic fibrosis (CF) and are frequently caused by Pseudomonas aeruginosa, resulting in chronic lung inflammation and fibrosis. The progression of multidrug-resistant strains of P. aeruginosa and alterations in the pharmacokinetics of many antibiotics in CF make optimal antimicrobial therapy a challenge, as reflected by high between- and inter-individual variability (IIV).
This review provides a synthesis of population pharmacokinetic models for various antibiotics prescribed in adult CF patients, and aims at identifying the most reported structural models, covariates and sources of variability influencing the dose-concentration relationship.
A literature search was conducted using the PubMed database, from inception to August 2020, and articles were retained if they met the inclusion/exclusion criteria.
A total of 19 articles were included in this review. One-, two- and three-compartment models were reported to best describe the pharmacokinetics of various antibiotics. The most common covariates were lean body mass and creatinine clearance. After covariate inclusion, the IIV (range) in total body clearance was 27.2% (10.40-59.7%) and 25.9% (18.0-33.9%) for β-lactams and aminoglycosides, respectively. IIV in total body clearance was estimated at 36.3% for linezolid and 22.4% for telavancin. The IIV (range) in volume of distribution was 29.4% (8.8-45.9%) and 15.2 (11.6-18.0%) for β-lactams and aminoglycosides, respectively, and 26.9% for telavancin. The median (range) of residual variability for all studies, using a combined (proportional and additive) model, was 12.7% (0.384-30.80%) and 0.126 mg/L (0.007-1.88 mg/L), respectively.
This is the first review that highlights key aspects of different population pharmacokinetic models of antibiotics prescribed in adult CF patients, effectively proposing relevant information for clinicians and researchers to optimize antibiotic therapy in CF.
下呼吸道感染在囊性纤维化（CF）成年患者中很常见，通常由铜绿假单胞菌引起，导致慢性肺炎症和纤维化。铜绿假单胞菌多药耐药株的进展和 CF 中许多抗生素药代动力学的改变使得优化抗菌治疗成为一项挑战，这反映在个体间和个体内变异性（IIV）高。
本综述综合了 CF 成年患者中各种抗生素的群体药代动力学模型，旨在确定最常报道的结构模型、协变量和影响剂量-浓度关系的变异性来源。
使用 PubMed 数据库进行文献检索，从开始到 2020 年 8 月，并保留符合纳入/排除标准的文章。
本综述共纳入 19 篇文章。一、二和三房室模型被报道为描述各种抗生素药代动力学的最佳模型。最常见的协变量是瘦体重和肌酐清除率。协变量纳入后，β-内酰胺类和氨基糖苷类抗生素的总清除率的个体内变异性（范围）分别为 27.2%（10.40-59.7%）和 25.9%（18.0-33.9%）。利奈唑胺和替考拉宁的总清除率个体内变异性分别估计为 36.3%和 22.4%。β-内酰胺类和氨基糖苷类抗生素的分布容积的个体内变异性分别为 29.4%（8.8-45.9%）和 15.2%（11.6-18.0%），替考拉宁为 26.9%。所有研究使用综合（比例和加性）模型的残余变异性中位数（范围）分别为 12.7%（0.384-30.80%）和 0.126mg/L（0.007-1.88mg/L）。
这是第一份突出 CF 成年患者中各种抗生素群体药代动力学模型关键方面的综述，为临床医生和研究人员提供了优化 CF 中抗生素治疗的相关信息。
