Journal Article

Pharmacokinetic studies of linezolid and teicoplanin in the critically ill

Tony Whitehouse, Jorge A. Cepeda, Rob Shulman, Leon Aarons, Ricardo Nalda-Molina, Caroline Tobin, Alasdair MacGowan, Steve Shaw, Chris Kibbler, Mervyn Singer and A. Peter R. Wilson

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 55, issue 3, pages 333-340
Published in print March 2005 | ISSN: 0305-7453
Published online March 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki014
Pharmacokinetic studies of linezolid and teicoplanin in the critically ill

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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

Journal Article.  5442 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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