scaling beta lactam antimicrobial pharmacokinetics.pdf (1.1 MB)
Scaling beta-lactam antimicrobial pharmacokinetics from early life to old age
journal contribution
posted on 2023-06-09, 17:39 authored by Dagan O Lonsdale, Emma H Baker, Karin Kipper, Charlotte Barker, Barbara PhilipsBarbara Philips, Andrew Rhodes, Mike Sharland, Joseph F StandingAIMS Beta-lactam dose optimization in critical care is a current priority. We aimed to review the pharmacokinetics (PK) of three commonly used beta-lactams (amoxicillin ± clavulanate, piperacillin-tazobactam and meropenem) to compare PK parameters reported in critically and noncritically ill neonates, children and adults, and to investigate whether allometric and maturation scaling principles could be applied to describe changes in PK parameters through life. METHODS A systematic review of PK studies of the three drugs was undertaken using MEDLINE and EMBASE. PK parameters and summary statistics were extracted and scaled using allometric principles to 70 kg individual for comparison. Pooled data were used to model clearance maturation and decline using a sigmoidal (Hill) function. RESULTS A total of 130 papers were identified. Age ranged from 29 weeks to 82 years and weight from 0.9-200 kg. PK parameters from critically ill populations were reported with wider confidence intervals than those in healthy volunteers, indicating greater PK variability in critical illness. The standard allometric size and sigmoidal maturation model adequately described increasing clearance in neonates, and a sigmoidal model was also used to describe decline in older age. Adult weight-adjusted clearance was achieved at approximately 2 years postmenstrual age. Changes in volume of distribution were well described by the standard allometric model, although amoxicillin data suggested a relatively higher volume of distribution in neonates. CONCLUSIONS Critical illness is associated with greater PK variability than in healthy volunteers. The maturation models presented will be useful for optimizing beta-lactam dosing, although a prospective, age-inclusive study is warranted for external validation.
History
Publication status
- Published
File Version
- Accepted version
Journal
British Journal of Clinical PharmacologyISSN
0306-5251Publisher
WIleyExternal DOI
Issue
2Volume
85Page range
316-346Department affiliated with
- BSMS Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2019-05-15First Open Access (FOA) Date
2019-09-03First Compliant Deposit (FCD) Date
2019-05-15Usage metrics
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