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

Authors Wu X, Tang Y, Zhang X, Wu C, Kong L

Received 20 March 2018

Accepted for publication 5 May 2018

Published 11 June 2018 Volume 2018:12 Pages 1679—1684

DOI https://doi.org/10.2147/DDDT.S168757

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Georgios D. Panos


Xiaofei Wu,1 Yan Tang,1 Xiaohua Zhang,1 Chenchen Wu,2 Lingti Kong3

1Department of Emergency Internal Medicine, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 2Department of Endocrinology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, People’s Republic of China

Objective: We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of linezolid in patients who had suffered cerebral hemorrhage after lateral ventricular drainage.
Materials and methods: 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).
Results: 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 (AUC0–24 h)/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.
Conclusions: 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.

Keywords: linezolid, cerebral hemorrhage, plasma, cerebrospinal fluid, pharmacokinetics, pharmacodynamics, Monte Carlo simulation

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