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Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology

Barker, CI; Germovsek, E; Hoare, RL; Lestner, JM; Lewis, J; Standing, JF; (2014) Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology. Advanced Drug Delivery Reviews , 73 pp. 127-139. 10.1016/j.addr.2014.01.002. Green open access

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Abstract

Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose-concentration-effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future.

Type: Article
Title: Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.addr.2014.01.002
Publisher version: http://dx.doi.org/10.1016/j.addr.2014.01.002
Language: English
Additional information: © 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Keywords: Antibacterial, Antifungal, Antimicrobial, Antiviral (and antiretrovirals), HIV viral and T-cell dynamics, Immune reconstitution, Non-linear mixed effects (NLME), Paediatrics, Pharmacokinetics/pharmacodynamics (PKPD)
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1418215
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