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General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review

Target controlled infusion (TCI) is a clinically-available and widely-used computer-controlled method of drug administration, adjusting the drug titration towards user selected plasma- or effect-site concentrations, calculated according to pharmacokinetic-pharmacodynamic (PKPD) models. Although this...

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Autores principales: Vandemoortele, Ophélie, Hannivoort, Laura N., Vanhoorebeeck, Florian, Struys, Michel M. R. F., Vereecke, Hugo E. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101974/
https://www.ncbi.nlm.nih.gov/pubmed/35566617
http://dx.doi.org/10.3390/jcm11092487
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author Vandemoortele, Ophélie
Hannivoort, Laura N.
Vanhoorebeeck, Florian
Struys, Michel M. R. F.
Vereecke, Hugo E. M.
author_facet Vandemoortele, Ophélie
Hannivoort, Laura N.
Vanhoorebeeck, Florian
Struys, Michel M. R. F.
Vereecke, Hugo E. M.
author_sort Vandemoortele, Ophélie
collection PubMed
description Target controlled infusion (TCI) is a clinically-available and widely-used computer-controlled method of drug administration, adjusting the drug titration towards user selected plasma- or effect-site concentrations, calculated according to pharmacokinetic-pharmacodynamic (PKPD) models. Although this technology is clinically available for several anaesthetic drugs, the contemporary commercialised PKPD models suffer from multiple limitations. First, PKPD models for anaesthetic drugs are developed using deliberately selected patient populations, often excluding the more challenging populations, such as children, obese or elderly patients, of whom the body composition or elimination mechanisms may be structurally different compared to the lean adult patient population. Separate PKPD models have been developed for some of these subcategories, but the availability of multiple PKPD models for a single drug increases the risk for invalid model selection by the user. Second, some models are restricted to the prediction of plasma-concentration without enabling effect-site controlled TCI or they identify the effect-site equilibration rate constant using methods other than PKPD modelling. Advances in computing and the emergence of globally collected databases has allowed the development of new “general purpose” PKPD models. These take on the challenging task of identifying the relationships between patient covariates (age, weight, sex, etc) and the volumes and clearances of multi-compartmental pharmacokinetic models applicable across broad populations from neonates to the elderly, from the underweight to the obese. These models address the issues of allometric scaling of body weight and size, body composition, sex differences, changes with advanced age, and for young children, changes with maturation and growth. General purpose models for propofol, remifentanil and dexmedetomidine have appeared and these greatly reduce the risk of invalid model selection. In this narrative review, we discuss the development, characteristics and validation of several described general purpose PKPD models for anaesthetic drugs.
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spelling pubmed-91019742022-05-14 General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review Vandemoortele, Ophélie Hannivoort, Laura N. Vanhoorebeeck, Florian Struys, Michel M. R. F. Vereecke, Hugo E. M. J Clin Med Review Target controlled infusion (TCI) is a clinically-available and widely-used computer-controlled method of drug administration, adjusting the drug titration towards user selected plasma- or effect-site concentrations, calculated according to pharmacokinetic-pharmacodynamic (PKPD) models. Although this technology is clinically available for several anaesthetic drugs, the contemporary commercialised PKPD models suffer from multiple limitations. First, PKPD models for anaesthetic drugs are developed using deliberately selected patient populations, often excluding the more challenging populations, such as children, obese or elderly patients, of whom the body composition or elimination mechanisms may be structurally different compared to the lean adult patient population. Separate PKPD models have been developed for some of these subcategories, but the availability of multiple PKPD models for a single drug increases the risk for invalid model selection by the user. Second, some models are restricted to the prediction of plasma-concentration without enabling effect-site controlled TCI or they identify the effect-site equilibration rate constant using methods other than PKPD modelling. Advances in computing and the emergence of globally collected databases has allowed the development of new “general purpose” PKPD models. These take on the challenging task of identifying the relationships between patient covariates (age, weight, sex, etc) and the volumes and clearances of multi-compartmental pharmacokinetic models applicable across broad populations from neonates to the elderly, from the underweight to the obese. These models address the issues of allometric scaling of body weight and size, body composition, sex differences, changes with advanced age, and for young children, changes with maturation and growth. General purpose models for propofol, remifentanil and dexmedetomidine have appeared and these greatly reduce the risk of invalid model selection. In this narrative review, we discuss the development, characteristics and validation of several described general purpose PKPD models for anaesthetic drugs. MDPI 2022-04-28 /pmc/articles/PMC9101974/ /pubmed/35566617 http://dx.doi.org/10.3390/jcm11092487 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Review
Vandemoortele, Ophélie
Hannivoort, Laura N.
Vanhoorebeeck, Florian
Struys, Michel M. R. F.
Vereecke, Hugo E. M.
General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review
title General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review
title_full General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review
title_fullStr General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review
title_full_unstemmed General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review
title_short General Purpose Pharmacokinetic-Pharmacodynamic Models for Target-Controlled Infusion of Anaesthetic Drugs: A Narrative Review
title_sort general purpose pharmacokinetic-pharmacodynamic models for target-controlled infusion of anaesthetic drugs: a narrative review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101974/
https://www.ncbi.nlm.nih.gov/pubmed/35566617
http://dx.doi.org/10.3390/jcm11092487
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