Wei Yongli, Zhang He, Fu Maowu, Ma Rui, Li Ronghui, Kong Lingti
Grade Three Laboratory of Traditional Chinese Medicine Preparation of the National Administration of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People's Republic of China.
Department of Neurosurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People's Republic of China.
Infect Drug Resist. 2022 Apr 8;15:1733-1742. doi: 10.2147/IDR.S357300. eCollection 2022.
The objective of this study was to perform pharmacokinetics/pharmacodynamics (PK/PD) analysis of linezolid in patients with intracerebral hemorrhage and to provide suggestions regarding dosing and treatment regimens.
Ten patients with cerebral hemorrhage and pulmonary infection were enrolled in this study. Plasma and sputum samples were obtained at specific time points after the seventh infusion. Linezolid concentration was measured using HPLC, and PK parameters were calculated using the non-compartmental model. The probability of target attainment (PTA) and the cumulative fraction of response (CFR) in response to different dosing regimens (1200 mg/900 mg/600 mg/300 mg, q12h) were calculated based on the ratio of area under the curve to minimum inhibitory concentration (AUC/MIC).
The C and AUC of linezolid were 12.89 μg/mL and 70.42 h·μg/mL for plasma, and 16.48 μg/mL and 92.95 h·μg/mL for sputum. The average penetration rate of linezolid in sputum, as represented by the ratio of AUC, was 131.99%. In response to the conventional dosing regimen (600mg, q12h), the PTA in the plasma or sputum was >90% only when MIC was ≤1 mg/L. Linezolid had the highest CFR against , followed by and , with the lowest value for .
This was the first study to evaluate PK/PD of linezolid in plasma and in the lungs of patients with cerebral hemorrhage and may assist in selecting appropriate dosing regimens for linezolid in these patients.
本研究的目的是对脑出血患者进行利奈唑胺的药代动力学/药效学（PK/PD）分析，并就给药剂量和治疗方案提供建议。
本研究纳入了10例脑出血合并肺部感染的患者。在第七次输注后的特定时间点采集血浆和痰液样本。采用高效液相色谱法测定利奈唑胺浓度，并使用非房室模型计算PK参数。根据曲线下面积与最低抑菌浓度之比（AUC/MIC）计算不同给药方案（1200mg/900mg/600mg/300mg，每12小时一次）的达标概率（PTA）和累积反应分数（CFR）。
利奈唑胺血浆C和AUC分别为12.89μg/mL和70.42h·μg/mL，痰液中分别为16.48μg/mL和92.95h·μg/mL。以AUC之比表示的利奈唑胺在痰液中的平均穿透率为131.99%。对于传统给药方案（600mg，每12小时一次），仅当MIC≤1mg/L时，血浆或痰液中的PTA>90%。利奈唑胺对[具体病菌名称未给出]的CFR最高，其次是[具体病菌名称未给出]和[具体病菌名称未给出]，对[具体病菌名称未给出]的CFR最低。
这是第一项评估利奈唑胺在脑出血患者血浆和肺部PK/PD的研究，可能有助于为这些患者选择合适的利奈唑胺给药方案。
