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


Corti, Natascia; Rudiger, Alain; Chiesa, Alessandro; Marti, Isabelle; Jetter, Alexander; Rentsch, Katharina; Müller, Daniel; Béchir, Markus; Maggiorini, Marco (2013). Pharmacokinetics of daily daptomycin in critically ill patients undergoing continuous renal replacement therapy. Chemotherapy, 59(2):143-151.

Abstract

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.

Abstract

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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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Intensive Care Medicine
04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
04 Faculty of Medicine > University Hospital Zurich > Institute of Anesthesiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:2013
Deposited On:28 Jan 2014 12:17
Last Modified:08 Dec 2017 03:07
Publisher:Karger
ISSN:0009-3157
Publisher DOI:https://doi.org/10.1159/000353400
PubMed ID:24051895

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