University of Sussex
Browse
- No file added yet -

Population pharmacokinetic study of benzylpenicillin in critically unwell adults

Download (1.61 MB)
journal contribution
posted on 2023-06-10, 06:44 authored by Reya V Shah, Karin Kipper, Emma H Baker, Charlotte IS Barker, Isobel Oldfield, Barbara PhilipsBarbara Philips, Atholl Johnston, Jeffrey Lipman, Andrew Rhodes, Marina Basarab, Mike Sharland, Sarraa Almahdi, Rachel M Wake, Joseph F Standing, Dagan O Lonsdale
Pharmacokinetics are highly variable in critical illness, and suboptimal antibiotic exposure is associated with treatment failure. Benzylpenicillin is a commonly used beta-lactam antibiotic, and pharmacokinetic data of its use in critically ill adults are lacking. We performed a pharmacokinetic study of critically unwell patients receiving benzylpenicillin, using data from the ABDose study. Population pharmacokinetic modelling was undertaken using NONMEM version 7.5, and simulations using the final model were undertaken to optimize the pharmacokinetic profile. We included 77 samples from 12 participants. A two-compartment structural model provided the best fit, with allometric weight scaling for all parameters and a creatinine covariate effect on clearance. Simulations (n = 10,000) demonstrated that 25% of simulated patients receiving 2.4 g 4-hourly failed to achieve a conservative target of 50% of the dosing interval with free drug above the clinical breakpoint MIC (2 mg/L). Simulations demonstrated that target attainment was improved with continuous or extended dosing. To our knowledge, this study represents the first full population PK analysis of benzylpenicillin in critically ill adults.

History

Publication status

  • Published

File Version

  • Published version

Journal

Antibiotics

ISSN

2079-6382

Publisher

MDPI AG

Issue

4

Volume

12

Page range

643-643

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2023-04-14

First Open Access (FOA) Date

2023-04-14

First Compliant Deposit (FCD) Date

2023-04-14

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC