Yongli Wei1, He Zhang1, Maowu Fu2, Rui Ma1, Ronghui Li2, Lingti Kong3. 1. 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. 2. Department of Neurosurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People's Republic of China. 3. Department of Pharmacy, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People's Republic of China.
Abstract
Purpose: 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. Patients and Methods: 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). Results: The 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. Conclusion: 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.
Purpose: 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. Patients and Methods: 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). Results: The 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. Conclusion: 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.
Authors: Andre C Kalil; Mark L Metersky; Michael Klompas; John Muscedere; Daniel A Sweeney; Lucy B Palmer; Lena M Napolitano; Naomi P O'Grady; John G Bartlett; Jordi Carratalà; Ali A El Solh; Santiago Ewig; Paul D Fey; Thomas M File; Marcos I Restrepo; Jason A Roberts; Grant W Waterer; Peggy Cruse; Shandra L Knight; Jan L Brozek Journal: Clin Infect Dis Date: 2016-07-14 Impact factor: 9.079
Authors: Gennaro De Pascale; Serena Fortuna; Mario Tumbarello; Salvatore Lucio Cutuli; MariaSole Vallecoccia; Teresa Spanu; Giuseppe Bello; Luca Montini; Mariano Alberto Pennisi; Pierluigi Navarra; Massimo Antonelli Journal: Intensive Care Med Date: 2014-11-21 Impact factor: 17.440