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Adv Drug Deliv Rev. 2014 Jun;73:127-39. doi: 10.1016/j.addr.2014.01.002. Epub 2014 Jan 17.

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology.

Author information

1
Paediatric Infectious Diseases Research Group, Division of Clinical Sciences, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK; Infectious Diseases and Microbiology Unit, University College London, Institute of Child Health, London WC1N 1EH, UK.
2
Infectious Diseases and Microbiology Unit, University College London, Institute of Child Health, London WC1N 1EH, UK.
3
Infectious Diseases and Microbiology Unit, University College London, Institute of Child Health, London WC1N 1EH, UK; CoMPLEX, University College London, Physics Building, Gower Street, London WC1E 6BT, UK.
4
Paediatric Infectious Diseases Research Group, Division of Clinical Sciences, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK; Faculty of Medicine, Imperial College London, London, UK.
5
Infectious Diseases and Microbiology Unit, University College London, Institute of Child Health, London WC1N 1EH, UK; CoMPLEX, University College London, Physics Building, Gower Street, London WC1E 6BT, UK. Electronic address: j.standing@ucl.ac.uk.

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.

KEYWORDS:

Antibacterial; Antifungal; Antimicrobial; Antiviral (and antiretrovirals); HIV viral and T-cell dynamics; Immune reconstitution; Non-linear mixed effects (NLME); Paediatrics; Pharmacokinetics/pharmacodynamics (PKPD)

PMID:
24440429
PMCID:
PMC4076844
DOI:
10.1016/j.addr.2014.01.002
[Indexed for MEDLINE]
Free PMC Article

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