Pharmacokinetics of daily daptomycin in critically ill patients undergoing continuous renal replacement therapy.
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).


CONCLUSIONS
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.
Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland.
Natascia
N
Corti
Alain
A
Rudiger
Alessandro
A
Chiesa
Isabelle
I
Marti
Alexander
A
Jetter
Katharina
K
Rentsch
Daniel
D
Müller
Markus
M
Béchir
Marco
M
Maggiorini
D000368:Aged; D019540:Area Under Curve; D016638:Critical Illness; D017576:Daptomycin / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D017582:Renal Replacement Therapy
D017576:Daptomycin