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Population Pharmacokinetic Study of Benzylpenicillin in Critically Unwell Adults

Shah, Reya V; Kipper, Karin; Baker, Emma H; Barker, Charlotte IS; Oldfield, Isobel; Philips, Barbara J; Johnston, Atholl; ... Lonsdale, Dagan O; + view all (2023) Population Pharmacokinetic Study of Benzylpenicillin in Critically Unwell Adults. Antibiotics , 12 (4) , Article 643. 10.3390/antibiotics12040643. Green open access

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Abstract

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.

Type: Article
Title: Population Pharmacokinetic Study of Benzylpenicillin in Critically Unwell Adults
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/antibiotics12040643
Publisher version: https://doi.org/10.3390/antibiotics12040643
Language: English
Additional information: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Keywords: benzylpenicillin; pharmacokinetics; critical illness; beta-lactam; antibiotic; NONMEM
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10168329
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