Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center.

Details

Serval ID
serval:BIB_936107FB37E5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center.
Journal
Antimicrobial agents and chemotherapy
Author(s)
Fournier A., Goutelle S., Que Y.A., Eggimann P., Pantet O., Sadeghipour F., Voirol P., Csajka C.
ISSN
1098-6596 (Electronic)
ISSN-L
0066-4804
Publication state
Published
Issued date
09/2018
Peer-reviewed
Oui
Volume
62
Number
9
Pages
e00505-18
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The objective of this study was to investigate the population pharmacokinetics (PK) of amoxicillin in ICU burn patients and the optimal dosage regimens. This was a prospective study involving 21 consecutive burn patients receiving amoxicillin. PK data were analyzed using nonlinear mixed-effects modeling. Monte-Carlo simulations assessed the influence of various amoxicillin dosage regimens with identified covariates on the probability to achieve a target (PTA) value of time during which free amoxicillin concentrations in plasma exceeded the MIC ( <i>f</i> T>MIC). A two-compartment model best described the data. Creatinine clearance (CL <sub>CR</sub> ) and body weight (BW) influenced amoxicillin CL and central volume of distribution ( <i>V</i> <sub>1</sub> ), respectively. The median CL <sub>CR</sub> (Cockcroft-Gault formula) was high (128 ml/min), with 25% of patients having CL <sub>CR</sub> s of >150 ml/min. The CL, <i>V</i> <sub>1</sub> , and half-life ( <i>t</i> <sub>1/2</sub> ) values at steady state for a patient with a CL <sub>CR</sub> of 110 ml/min and BW of 70 kg were 13.6 liters/h, 9.7 liters, and 0.8 h, respectively. Simulations showed that a target <i>f</i> T>MIC of ≥50% was achieved (PTA > 90%) with standard amoxicillin dosage regimens (1 to 2 g every 6 to 8 h [q6-8h]) when the MIC was low (<1 mg/liter). However, increased dosages of up to 2 g/4 h were necessary in patients with augmented CL <sub>R</sub> s or higher MICs. Prolonging amoxicillin infusion from 30 min to 2 h had a favorable effect on target attainment. In conclusion, this population analysis shows an increased amoxicillin CL and substantial CL PK variability in burn patients compared to literature data with nonburn patients. Situations of augmented CL <sub>CR</sub> and/or high bacterial MIC target values may require dosage increases and longer infusion durations. (This study has been registered at ClinicalTrials.gov under identifier NCT01965340.).
Keywords
amoxicillin, burn patients, pharmacokinetics, population pharmacokinetics
Pubmed
Web of science
Open Access
Yes
Create date
23/07/2018 17:05
Last modification date
20/08/2019 15:56
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