| Περίληψη: | Pharmacokinetics is the process that determines the drug amount in the
body over time, which is essential for understanding the pharmacodynamics of
a drug. It is a study of drug disposition in the body and focuses on the changes
in the blood drug concentration. The pharmacokinetic characteristics can be
quantitatively expressed by its parameters, such as the elimination rate
constant (denoted as K), terminal half-life (t1/2), apparent volume of distribution
(Vd) and total clearance rate (CL). These parameters are important to define
the fate of a drug after administration by a particular route.
Pharmacokinetic study is mainly performed by the compartmental or
non-compartmental analysis. The non-compartmental analysis is the most
popular method in pharmacokinetic studies at the present time.
The noncompartmental analysis (NCA) is similar to kinetic analyses
used in other scientific disciplines, such as chemical kinetics and
chromatographic theory, both of which are analyzed basing on statistical
moments principles. The noncompartmental method evaluates the exposure of
a drug by estimating the area under the curve (AUC) of a drug concentrationtime graph, which is more versatile in that it relies very little on the
compartmental model or the in vivo process of the drugs.
The compartmental method estimates the concentration-time graph
using kinetic models. Several functional models have been developed in order
to simplify the study of pharmacokinetics, and these models are based on the
consideration of the organism as a number of related compartments.
Modelling of the pharmacokinetic and pharmacodynamic (PK/PD)
characteristics of drugs can support the optimization of dosing regimens.
PK/PD of drugs describe the relationship between efficacy, the in vitro
susceptibility of a drug to the microorganism (usually expressed as MIC,
minimal inhibitory concentration) and the in vivo exposure to the drug, which
relies on the PK and the dose.
Sufficient understanding of the interpretation of modelling results is
essential for good implementation of these dosing recommendations.
Therefore, this project provides background information on the PK/PD
principles of antibiotics and the different approaches of analyzing PK/PD data
with the objective to understand the published population PK models and their
clinical applications.
Last but not least, discusses the clinical applications of population PK
models of drugs (setting clinical MIC breakpoints and therapeutic drug
monitoring) including challenges regarding the interpretation of modelling
results.
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