Journal Article

Pharmacokinetics and pharmacodynamics of linezolid in plasma/cerebrospinal fluid in patients with cerebral hemorrhage after lateral ventricular drainage by Monte Carlo simulation

Wu, Chenchen, Zhang, Xiaohua, Tang, Yan, Kong, Lingti, Wu, Xiaofei

2018

Overview

We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of linezolid in patients who had suffered cerebral hemorrhage after lateral ventricular drainage. Ten patients with cerebral hemorrhage after lateral ventricular drainage with stroke-associated pneumonia who were given linezolid were enrolled. Plasma and cerebrospinal fluid (CSF) samples were taken at appropriate intervals after the first administration of linezolid and assayed by high-performance liquid chromatography (HPLC). Then, PK parameters were estimated, and a Monte Carlo simulation was used to calculate the probability of target attainments (PTAs) for linezolid achieving the PK/PD index at different minimal inhibitory concentrations (MICs). The maximum concentration of linezolid in plasma and CSF was reached at 1.00 h and 3.10 h, respectively. The average penetration of linezolid in CSF was 56.81%. If the area under the plasma concentration vs time curve from zero to the final sampling time (AUC )/MIC ≥ 59.1 was applied as a parameter, the PTA of linezolid in plasma could provide good coverage (PTA ≥ 90%) only for pathogens with a MIC of ≤2 μg/mL, whereas it could be achieved in CSF with a MIC of ≤1 μg/mL. If %T > MIC ≥ 40% was applied as a parameter, the PTA of linezolid in plasma/CSF could provide good coverage if the MIC was ≤4 μg/mL. For patients with infection of the central nervous system and who are sensitive to the drug, the usual dosing regimens of linezolid can achieve a good therapeutic effect. However, for critically ill or drug-resistant patients, an increase in dose, the frequency of administration, or longer infusion may be needed to improve the curative effect.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Medical Press
• Subject: Aged / Anti-Bacterial Agents - administration & dosage / Anti-Bacterial Agents - blood / Anti-Bacterial Agents - cerebrospinal fluid / Anti-Bacterial Agents - pharmacokinetics / Bacterial infections / Brain hemorrhage / Care and treatment / Central nervous system / Central Nervous System Bacterial Infections - blood / Central Nervous System Bacterial Infections - cerebrospinal fluid / Central Nervous System Bacterial Infections - drug therapy / Central Nervous System Bacterial Infections - microbiology / Cerebral hemorrhage / Cerebral Hemorrhage - etiology / Cerebrospinal fluid / Chromatography / Chromatography, High Pressure Liquid / Computer Simulation / Dosage / Drainage - adverse effects / Drug Dosage Calculations / Drug Monitoring - methods / Drug resistance / Edema / FDA approval / Female / Health aspects / Hemorrhage / High performance liquid chromatography / Hospitals / Humans / Internal medicine / Lateral Ventricles - surgery / Linezolid / Linezolid - administration & dosage / Linezolid - blood / Linezolid - cerebrospinal fluid / Linezolid - pharmacokinetics / Liquid chromatography / Male / Methicillin / Middle Aged / Minimum inhibitory concentration / Models, Biological / Monte Carlo Method / Monte Carlo methods / Monte Carlo simulation / Mortality / Nervous system / Nosocomial infections / Original Research / Parameter estimation / Pathogenic microorganisms / Patients / Pharmacodynamics / Pharmacokinetics / Pharmacology / Plasma / Pneumonia / Staphylococcus infections / Ventricle / Wound drainage