Critical Care Medicine

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Critical Care Medicine:
doi: 10.1097/CCM.0b013e3181fa36fb
Clinical Investigations

Daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis

Vilay, A. Mary PharmD; Grio, Maricor MD, MS; DePestel, Daryl D. PharmD; Sowinski, Kevin M. PharmD, FCCP; Gao, Lihong PhD; Heung, Michael MD; Salama, Noha N. PhD; Mueller, Bruce A. PharmD, FCCP, FASN



In the article on page 19 in the January 2011 issue of the Journal, there was a transcription error in Table 3 for subject 7. The Vss should have been 0.21 L/kg, resulting in a means ± sd of 0.20 ± 0.08 L/kg.

Critical Care Medicine. 39(5):1247, May 2011.

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Objective: To investigate daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis to develop dosing recommendations.

Design: Prospective, open-label pharmacokinetic study.

Setting: Intensive care units located within a teaching medical center.

Patients: Eight adults with known/suspected Gram-positive infections receiving continuous venovenous hemodialysis and daptomycin.

Interventions: Daptomycin at 8 mg/kg intravenously over 30 mins. Serial blood and effluent samples were collected over the next 48 hrs. Daptomycin protein binding was determined by equilibrium dialysis. Daptomycin continuous venovenous hemodialysis transmembrane clearance was determined by dividing daptomycin effluent by serum concentrations and multiplying by mean effluent production rate for each subject. Equations describing a two-compartment, open-pharmacokinetic model were fitted to each subject's daptomycin concentration-time data and pharmacokinetic parameters were determined by standard methods. Serum concentration-time profiles were simulated for two daptomycin regimens (8 mg/kg every 48 hrs and 4 mg/kg every 24 hrs).

Measurements and Main results: A total of 7.7 ± 0.6 mg/kg (mean ± sd) of daptomycin was administered, resulting in an observed peak concentration of 81.2 ± 19.0 μg/mL. Daptomycin steady-state volume of distribution (0.23 ± 0.14 L/kg) and free fraction (17.5% ± 5.0%) were increased in critically ill subjects receiving continuous venovenous hemodialysis compared with previous values reported in healthy volunteers. Daptomycin transmembrane clearance (6.3 ± 2.9 mL/min) accounted for more than half of total clearance (11.3 ± 4.7 mL/min). Simulations demonstrated 8 mg/kg daptomycin every 48 hrs would result in higher peak (88.8 ± 20.0 μg/mL vs. 53.0 ± 12.3 μg/mL) and lower trough concentrations (7.2 ± 5.2 μg/mL vs. 12.3 ± 5.1 μg/mL) than 4 mg/kg every 24 hrs.

Conclusions: Daptomycin at 8 mg/kg every 48 hrs in critically ill patients receiving continuous venovenous hemodialysis resulted in good drug exposure, achieved high peak concentrations to maximize daptomycin's concentration-dependent activity, and resulted in trough concentration that would minimize the risk of myopathy. Identifier: NCT00663403.

© 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

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