Pharmacokinetic concepts revisited: Basic and applied

Patel, Kashyap and Kirkpatrick, Carl M. J. (2011) Pharmacokinetic concepts revisited: Basic and applied. Current Pharmaceutical Biotechnology, 12 12: 1983-1990. doi:10.2174/138920111798808400

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Author Patel, Kashyap
Kirkpatrick, Carl M. J.
Title Pharmacokinetic concepts revisited: Basic and applied
Journal name Current Pharmaceutical Biotechnology   Check publisher's open access policy
ISSN 1389-2010
1873-4316
Publication date 2011-12
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2174/138920111798808400
Volume 12
Issue 12
Start page 1983
End page 1990
Total pages 8
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Collection year 2012
Language eng
Formatted abstract
Pathophysiological changes are common in critically ill patients, and can alter the time course of drug concentrations following dosing. The latter is termed pharmacokinetics (PK), and describes the relationship between dose administered and drug concentrations in plasma. Thus, modifications in PK necessitate dose adjustment, to optimize drug therapy in critical care. An understanding of basic PK principles is therefore required, to improve dosage guidelines in the population treated. Here, we define the key PK parameters, with specific application to critically ill patients. We then overview the methods used for PK analysis, in both research and in the clinical setting. Traditionally, non-compartmental and standard two-stage approaches have been used in small groups of patients with similar demographics and pathophysiology. However, these methods require intensive sampling, and do not explicitly describe inter-individual variability, or errors associated with measurement or sampling. Population PK (POPPK) modelling is advantageous in this regard, and can use both sparse and rich datasets to provide accurate estimates for between-subject variability (BSV). In addition, POPPK can explore patient parameter-covariate relationships, to account for some of the BSV in PK. This information is useful with assisting individualized dosing in the clinic. While the above methods are suitable for research, they are too time-consuming in the clinical setting, and Bayesian approaches have been adopted to optimize dosing. These methods, together with POPPK and appropriate study design are recommended for improved dosing in critical care.
Keyword Bayesian methods
Clearance
Critically ill
Dose optimization
Pharmacokinetics
Population modeling
Volume of distribution
Critically-ill patients
Target concentration intervention
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2012 Collection
School of Pharmacy Publications
 
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