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. 2018 Jun 11:12:1679-1684.
doi: 10.2147/DDDT.S168757. eCollection 2018.

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

Xiaofei Wu  1 , Yan Tang  1 , Xiaohua Zhang  1 , Chenchen Wu  2 , Lingti Kong  3
Affiliations

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

Xiaofei Wu et al. Drug Des Devel Ther. .

Abstract

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: Monte Carlo simulation; cerebral hemorrhage; cerebrospinal fluid; linezolid; pharmacodynamics; pharmacokinetics; plasma.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
HPLC chromatogram of linezolid from CSF at 3 h after the infusion. Abbreviations: HPLC, high-performance liquid chromatography; CSF, cerebrospinal fluid.
Figure 2
Figure 2
Plasma concentration–time curves of linezolid in patients. Each point represents the mean ± SD (N = 10).
Figure 3
Figure 3
Cerebrospinal-fluid concentration–time curves of linezolid in patients. Note: Each point represents the mean ± SD (n = 10).
See this image and copyright information in PMC

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