Department of Clinical Pharmacy, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
Division of Pulmonary and Critical Care Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Antimicrob Agents Chemother. 2018 Aug 27;62(9). doi: 10.1128/AAC.00550-18. Print 2018 Sep.
Over the past decade, the prevalence of infections involving methicillin-resistant (MRSA) in patients with cystic fibrosis (CF) has increased significantly. Tedizolid (TZD) demonstrates excellent activity against MRSA and a favorable safety profile. The pharmacokinetics of several antibiotics have been shown to be altered in CF patients. The purpose of this study was to characterize the pharmacokinetics of tedizolid in this population. Eleven patients with CF were randomized to receive tedizolid phosphate at 200 mg orally or intravenously once daily for 3 doses with a minimum 2-day washout, followed by crossover to the remaining dosage form. Plasma and expectorated sputum were collected following the third dose of each dosage form for analysis. Population pharmacokinetic analysis was performed using the maximum likelihood expectation maximization method, and the disposition of TZD was described by a two-compartment model. The sputum concentrations exceeded the unbound plasma concentrations with an estimated mean sputum-to-unbound plasma penetration ratio of 2.88 (coefficient of variation, 50.3%). The estimated population mean ± standard deviation of total clearance, central volume of distribution, and bioavailability were 9.72 ± 1.62 liters/h, 61.6 ± 6.94 liters, and 1.04 ± 0.232, respectively. The total clearance was higher in CF patients than in healthy volunteers; however, it was similar to published data for patients with complicated skin and skin structure infections (cSSSIs). This study demonstrates that the oral bioavailability of tedizolid is excellent in patients with CF and that the plasma pharmacokinetics are similar to those reported for patients with cSSSIs.
在过去的十年中，患有囊性纤维化 (CF) 的患者中耐甲氧西林金黄色葡萄球菌 (MRSA) 感染的患病率显著增加。替加环素 (TZD) 对 MRSA 具有出色的活性和良好的安全性。已经证明，几种抗生素的药代动力学在 CF 患者中发生了改变。本研究的目的是描述 TZD 在该人群中的药代动力学特征。11 例 CF 患者随机接受替加环素磷酸盐 200mg 口服或静脉注射，每日 1 次，连续 3 剂，洗脱期至少 2 天，然后交叉至其余剂型。每种剂型的第 3 剂后采集血浆和咳出的痰样进行分析。采用最大似然期望最大化法进行群体药代动力学分析，TZD 的分布用两室模型描述。痰浓度超过未结合血浆浓度，估计平均痰与未结合血浆穿透比为 2.88（变异系数，50.3%）。总清除率、中央分布容积和生物利用度的群体平均估计值 ± 标准偏差分别为 9.72 ± 1.62 升/小时、61.6 ± 6.94 升和 1.04 ± 0.232。CF 患者的总清除率高于健康志愿者；然而，它与患有复杂性皮肤和皮肤结构感染 (cSSSIs) 的患者的已发表数据相似。这项研究表明，替加环素在 CF 患者中的口服生物利用度极好，且其血浆药代动力学与报告的 cSSSIs 患者相似。
