Identification of subjects with low baseline variability in pharmacokinetic parameters in clinical trials using bioimpedance analysis

Actuality. Bioimpedancemetry allows the assessment of the body’s components and has virtually no negative consequences. Using the presented method, the authors proposed approaches designed to reduce the clinical trial sample’s pharmacokinetic heterogeneity. This is dictated by the results of previous studies that showed that routine clinical, laboratory, and instrumental indicators do not allow the selection of subjects with an initially lower variability of pharmacokinetic parameters.
Objective. This study aimed to assess the possibility of using data obtained during a screening examination and the bioimpedancemetry method to identify subjects with an initially lower level of pharmacokinetic parameter variability during a highly variable raltegravir clinical trial (n = 50).
Methodology. A four-period study of a highly variable raltegravir was conducted in 2024 in accordance with the Russian Federation’s regulatory and ethical requirements. Mathematical and statistical analyses of the results were performed using the R 4.4.3 and Statistica 10.0 packages, as well as Microsoft Excel 2013 for plotting graphs and tables. A staged assessment of the information content of several parameters measured as part of routine medical manipulations, measurements of raltegravir plasma concentration parameters, and bioimpedancemetry parameters was performed.
Results. The results of a two-stage analysis of the parameters of volunteers who used raltegravir in a clinical trial allowed us to establish that the use of bioimpedancemetry results in addition to the clinical and laboratory parameters obtained during the screening period significantly increases the efficiency of discrimination of subgroups with different levels of variability in the training sample from 82.1% (total group and subgroups) to 97.2% in the total group and up to 100% in the variable pharmacokinetics subgroup.

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