Population pharmacokinetics of daptomycin in critically ill patients with various degrees of renal impairment

Abstract Objectives The objective of this study was to characterize the pharmacokinetics of unbound and total concentrations of daptomycin in infected ICU patients with various degrees of renal impairment. From these results, the probability of attaining antimicrobial efficacy and the risks of toxic...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2019-01, Vol.74 (1), p.117-125
Main Authors: Grégoire, Nicolas, Marchand, Sandrine, Ferrandière, Martine, Lasocki, Sigismond, Seguin, Philippe, Vourc’h, Mickaël, Barbaz, Mathilde, Gaillard, Thomas, Launey, Yoann, Asehnoune, Karim, Couet, William, Mimoz, Olivier
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Anti-Bacterial Agents
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - adverse effects
Anti-Bacterial Agents - pharmacokinetics
Biostatistics
Critical Illness
Daptomycin
Daptomycin - administration & dosage
Daptomycin - adverse effects
Daptomycin - pharmacokinetics
Female
Humans
Life Sciences
Male
Microbial Sensitivity Tests
Middle Aged
Pharmaceutical sciences
Plasma
Plasma - chemistry
Renal Insufficiency
Urine
Urine - chemistry
Young Adult
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Summary:Abstract Objectives The objective of this study was to characterize the pharmacokinetics of unbound and total concentrations of daptomycin in infected ICU patients with various degrees of renal impairment. From these results, the probability of attaining antimicrobial efficacy and the risks of toxicity were assessed. Methods Twenty-four ICU patients with various renal functions and requiring treatment of complicated skin and soft-tissue infections, bacteraemia, or endocarditis with daptomycin were recruited. Daptomycin (Cubicin®) at 10 mg/kg was administered every 24 h for patients with creatinine clearance (CLCR) ≥30 mL/min and every 48 h for patients with CLCR 40 or >80) or toxicity (Cmin >24.3 mg/L) targets. Results Exposure to unbound daptomycin increased when the renal function decreased, thus increasing the probability of reaching the efficacy targets, but also the risk of toxicity. Modifications of the unbound fraction (fu) of daptomycin did not affect the pharmacokinetics of unbound daptomycin, but did affect the pharmacokinetics of total daptomycin. Conclusions Daptomycin at 10 mg/kg q24h allowed efficacy pharmacokinetic/pharmacodynamic targets for ICU patients with CLCR ≥30 mL/min to be reached. For patients with CLCR
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dky374