Multiple-dose pharmacokinetics of daptomycin during continuous venovenous haemodiafiltration.
J Antimicrob Chemother
; 67(4): 977-83, 2012 Apr.
Article
em En
| MEDLINE
| ID: mdl-22210754
ABSTRACT
OBJECTIVES:
Daptomycin is bactericidal against Gram-positive bacteria, with peak-dependent effect but trough-dependent toxicity. This study was performed to develop dosing recommendations in continuous venovenous haemodiaï¬ltration (CVVHDF). PATIENTS ANDMETHODS:
Nine critically ill patients in intensive care units of the Medical University Hospital of Vienna, requiring CVVHDF due to acute renal failure and antimicrobial treatment, were included. Blood and effluent samples were collected over 72 h to determine daptomycin concentrations by HPLC. Pharmacokinetic parameters were based on 10 sampling timepoints during the first 24 h, and peak and trough samples thereafter. An open two-compartment model was fitted to each subject's plasma concentration-time data. Simulations of serum concentration-time profiles after different doses and intervals were performed using ADAPT 5.RESULTS:
Peak plasma concentrations with 6 mg/kg daptomycin were 62.2 ± 16.2, 66.1 ± 17.3 and 78.5 ± 22.1 mg/L on days 1, 2 and 3, respectively. The total clearance was 6.1 ± 4.9 mL/min, and the elimination half-life was 17.8 ± 9.7 h. Daptomycin was filtrated and could therefore be measured in the effluent. Protein binding was lower than that seen in healthy volunteers. The unbound fraction was 16 ± 4.5%. All subjects maintained trough serum concentrations above 4 mg/L, at which relevant pathogens are considered daptomycin-susceptible. Accumulation resulted when daptomycin was given every 24 h. Simulation of 8 mg/kg daptomycin given every 48 h resulted in adequate levels without accumulation.CONCLUSIONS:
We recommend 8 mg/kg daptomycin every 48 h in patients on CVVHDF and therapeutic drug monitoring, if possible.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Bacterianas
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Hemofiltração
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Daptomicina
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Injúria Renal Aguda
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Antibacterianos
Tipo de estudo:
Guideline
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
/
Humans
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Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article