JAC Advance Access originally published online on February 10, 2005
Journal of Antimicrobial Chemotherapy 2005 55(3):333-340; doi:10.1093/jac/dki014
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JAC vol.55 no.3 © The British Society for Antimicrobial Chemotherapy 2005; all rights reserved
Pharmacokinetic studies of linezolid and teicoplanin in the critically ill
1Bloomsbury Institute of Intensive Care Medicine, Department of Medicine, University College London, London; Departments of 2 Clinical Microbiology, and 3 Pharmacy, University College London Hospitals, London; 4 School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester; 6 Department of Microbiology, Southmead Hospital, Bristol; 7 Intensive Care Unit and 8 Department of Medical Microbiology, Royal Free Hospital, London, UK; 5 Facultad de Farmacia, Universidad de Valencia, Valencia, Spain
* Correspondence address. Department of Clinical Microbiology, University College Hospital, 46 Cleveland Street, London W1T 4JF, UK. Tel: +44-207-380-9516; Fax: +44-207-636-6482; Email: peter.wilson{at}uclh.nhs.uk
Objectives: To determine the pharmacokinetic characteristics of linezolid and teicoplanin in critically ill patients.
Patients and methods: Serum was collected frequently during day 0 and then pre- and 1 h post-dose on days 1, 2, 3, 5, 7 and every third day thereafter during treatment. Serum linezolid concentrations were analysed using HPLC. Serum teicoplanin levels were analysed by fluorescence polarization immunoassay.
Results: A two-compartment model was required to characterize linezolid pharmacokinetics (n=28) and account for the accumulation seen after multiple dosing. The estimated clearance was 0.049 ±0.016 L/h/kg (±S.E.M. of estimate). At steady state (dosing interval 12 h), linezolid serum concentrations exceeded the breakpoint of 4 mg/L for 10.88 h (95% CI 10.09–11.66) after a 600 mg dose with an AUC/MIC of 92.4 (95% CI 57.2–127.7). Teicoplanin was best described by a two-compartment model (n=26). The clearance was 4.97±1.58 L/h. Serum levels exceeded the breakpoint of 4 mg/L for the entire dosing interval in all subjects (400 mg dose every 12 h) with an AUC/MIC of 399.3 (95% CI 329.6–469.0). However, only four of 14 exceeded trough serum concentrations of 10 mg/L. For both agents, trough levels were similar in those who survived and those who died.
Conclusions: Linezolid dosage at 600 mg every 12 h was adequate in the critically ill without need for adjustment for renal function. For teicoplanin, further study is needed to confirm if a trough of 10 mg/L is associated with a higher rate of cure than 5 mg/L. If so, serum drug assays would be needed to ensure a therapeutic level.
Keywords: critical care , pharmacokinetics , AUC , HPLC
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