Pharmacokinetic studies of linezolid and teicoplanin in the critically ill

• Published in: Journal of antimicrobial chemotherapy 2005-03, Vol.55 (3), p.333-340
• Main Authors: Whitehouse, Tony, Cepeda, Jorge A., Shulman, Rob, Aarons, Leon, Nalda-Molina, Ricardo, Tobin, Caroline, MacGowan, Alasdair, Shaw, Steve, Kibbler, Chris, Singer, Mervyn, Wilson, A. Peter R.
• Format: Article
• Language: English
• Subjects: Acetamides - pharmacokinetics; Acetamides - pharmacology; Adolescent; Adult; Aged; Aged, 80 and over; Antibiotics. Antiinfectious agents. Antiparasitic agents; Area Under Curve; AUC; Biological and medical sciences; critical care; Critical Illness; Double-Blind Method; Female; HPLC; Humans; Linezolid; Male; Medical sciences; Middle Aged; Models, Biological; Oxazolidinones - pharmacokinetics; Oxazolidinones - pharmacology; pharmacokinetics; Pharmacology. Drug treatments; Prospective Studies; Teicoplanin - pharmacokinetics; Teicoplanin - pharmacology
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dki014

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.