Abstract

PurposeThe 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.Patients and MethodsTen 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).ResultsThe Cmax 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 Streptococcus pneumoniae, followed by Enterococcus faecalis and Enterococcus faecium, with the lowest value for MRSA.ConclusionThis 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.

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