Calculation of pharmacokinetic parameters using Non-Compartmental Analysis (NCA)

• Κύριος συγγραφέας: Ρούσσου, Θεοδώρα
• Άλλοι συγγραφείς: Roussou, Theodora
• Γλώσσα: English
• Έκδοση: 2022
• Θέματα: Pharmacokinetics; Noncompartmental analysis (NCA); Φαρμακοκινητική; Διαμερισματική ανάλυση

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.