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

Fournier, Anne; Goutelle, Sylvain; Que, Yok-Ai; Eggimann, Philippe; Pantet, Olivier; Sadeghipour, Farshid; Voirol, Pierre; Csajka, Chantal (2018). Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center. Antimicrobial agents and chemotherapy, 62(9) American Society for Microbiology 10.1128/AAC.00505-18

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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 (T>MIC). A two-compartment model best described the data. Creatinine clearance (CL) and body weight (BW) influenced amoxicillin CL and central volume of distribution (), respectively. The median CL (Cockcroft-Gault formula) was high (128 ml/min), with 25% of patients having CLs of >150 ml/min. The CL, , and half-life () values at steady state for a patient with a CL 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 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 CLs 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 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.).

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care

UniBE Contributor:

Que, Yok-Ai

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0066-4804

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Mirella Aeberhard

Date Deposited:

05 Nov 2018 11:33

Last Modified:

04 Dec 2019 23:17

Publisher DOI:

10.1128/AAC.00505-18

PubMed ID:

29914948

Uncontrolled Keywords:

amoxicillin burn patients pharmacokinetics population pharmacokinetics

BORIS DOI:

10.7892/boris.120911

URI:

https://boris.unibe.ch/id/eprint/120911

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