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Published on: August 30, 2018
Pharmacokinetics of daily daptomycin in critically ill patients undergoing continuous renal replacement therapy
Natascia Corti1, Alain Rudiger, Alessandro Chiesa
1Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
Background:
The optimal daptomycin dosing regimen for critically ill patients undergoing continuous renal replacement therapy (CRRT) has still to be established.
Methods:
Daptomycin pharmacokinetics was determined in 9 patients after administration of 6 mg/kg/day over 5 days.
Results:
At steady state, which was reached by day 3, the area under the curve over 24 h (AUC24h) was 667.4 ± 356.6 mg·h/l, and the maximum concentration (Cmax) was 66.9 ±25.3 mg/l. Mean CRRT clearance accounted for 48% (range 32-67%) of total clearance (mean 10.2 ml/min, range 6.1-18 ml/min). Significant correlations were observed between Cmax, minimum concentration (Cmin) and AUC24h (R(2) = 0.91, p < 0.001, and R(2) = 0.94, p < 0.001) and between albumin plasma concentration and free daptomycin (R(2) = 0.7, p = 0.009).
Conclusion:
No significant accumulation occurred with a daily daptomycin dose of 6 mg/kg in patients undergoing CRRT with an effluent flow rate of >30 ml/kg/h. The quantification of trough concentrations (Cmin) appears to be a good surrogate to estimate AUC24h and to monitor daptomycin treatment in patients undergoing CRRT.
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