• DOI:10.5414/CP201626
• Corpus ID: 36616967

Plasma pharmacokinetics of daptomycin in critically ill patients with renal failure and undergoing CVVHD.

@article{Khadzhynov2011PlasmaPO,
  title={Plasma pharmacokinetics of daptomycin in critically ill patients with renal failure and undergoing CVVHD.},
  author={Dmytro Khadzhynov and Torsten Slowinski and Ina Lieker and Claudia D. Spies and Birgit Puhlmann and T K{\"o}nig and Alexander Uhrig and Karen E. Eggers and H H Neumayer and F Traunm{\"u}ller and Christian Joukhadar and Harm Peters},
  journal={International journal of clinical pharmacology and therapeutics},
  year={2011},
  volume={49 11},
  pages={
          656-65
        }
}

• D. Khadzhynov, T. Slowinski, +9 authors H. Peters
• Published 1 November 2011
• Medicine, Biology, Chemistry
• International journal of clinical pharmacology and therapeutics

BACKGROUND
Daptomycin is a novel antibiotic with primarily renal elimination.

METHODS
In an open-label, prospective trial, the pharmacokinetics of daptomycin after single (8 mg/kg BW) and multiple intravenous doses (4 mg/kg BW) at steady state were determined in critically ill, dialysis-dependent patients treated with continuous veno-venous hemodialysis (CVVHD). Daptomycin levels were determined by HPLC. Subjects with normal renal function received one dose of 4 mg/kg BW of daptomycin.

RESULTS
In the normal controls, daptomycin administration resulted in a mean maximum concentration (Cmax) of 60.7 ± 10.7 mg/l and an area under the time-versus-concentration curve from 0 to 24 h (AUC0-24) of 402 ± 56 mg × h/l. In the CVVHD-treated patients, a loading dose of 8 mg/kg lead to Cmax of 87.5 ± 15.0 mg/l, AUC0-24 of 537 ± 97 mg × h/l and AUC24-48 of 193 ± 69 mg × h/l, respectively. After multiple doses of 4 mg/kg every 48 h, Cmax was 41.8 ± 5.0 mg/l, AUC0-24 302 ± 43 mg × h/l and AUC 24-48 h 102 ± 24 mg × h/l, respectively. Approximately 40% of the daptomycin dose administered was removed by CVVHD. Mean plasma half-lives of daptomycin in patients were 2 - 3 times longer than in healthy controls.

CONCLUSIONS
The dosing regimen of 4 mg/kg TBW of daptomycin administered to CVVHD patients every 48 h is inappropriate to achieve effective antimicrobial plasma concentrations of daptomycin in the second half of the dosing interval (24 - 48 h). Doses of ≥ 4 mg/kg TBW administered intravenously every 24 h are necessary in CVVHD patients to assure that plasma daptomycin levels are comparably high to subjects with normal renal function and to avoid underdosing.