Intradialytic administration of daptomycin in end stage renal disease patients on hemodialysis

Abstract

Background and objectives: Infusion of intravenous antibiotics after hemodialysis (HD) may delay initiation of treatment for the next HD shift. Intradialytic administration of drugs such as vancomycin during the final hour of HD obviates these delays. Daptomycin has potent activity against Gram-positive bacteria, but the manufacturer recommends that the dose be infused after HD ends. This study determined the pharmacokinetics of intradialytically dosed daptomycin in patients with ESRD.

Design, setting, participants, & measurements: This prospective crossover study compared single-dose daptomycin (6 mg/kg, 30-min intravenous infusion) pharmacokinetics administered after HD versus during the last part of HD with high-permeability (HP) and low-permeability (LP) dialyzers to seven patients who had ESRD and were on thrice-weekly HD. Serial blood samples were collected to determine daptomycin serum concentrations and protein binding. Statistical analysis was done using linear mixed model analysis.

Results: The maximum serum concentration observed with a 6 mg/kg post-HD dose was 61.1 +/- 7.6 microg/ml with a mean protein binding of 89.2%. Intradialytic daptomycin administration resulted in reduced maximum serum concentration and area under the curve values that were approximately 12 to 20% lower when administered during HD with LP dialyzers and approximately 35% lower with HP dialyzers.

Conclusions: Intradialytic daptomycin administration during the last 30 min of HD is feasible, provided that larger dosages are used to compensate for intradialytic drug loss. On the basis of our findings, intradialytic doses of approximately 7 mg/kg (LP) or approximately 9 mg/kg (HP) theoretically should be bioequivalent to 6 mg/kg infused after HD. The calculated dosages are mathematically driven and must be validated in prospective clinical trials.

Figure 1.

Mean ± SD daptomycin (6 mg/kg) serum concentrations versus time profile after 30-min intravenous infusion when administered (1) after hemodialysis (HD; ) versus (2) infused during the last part of HD with high-permeability (○) and (3) low-permeability (•) dialyzers to seven patients who had ESRD and were on thrice-weekly HD.