Ведомости Научного центра экспертизы средств медицинского применения (Mar 2021)
Use of Biomarkers in Pharmacokinetics Studies of Medicinal Products of Natural Origin
Abstract
Abstract. Medicinal products of natural origin are widely used by virtue of their pharmacological efficacy and relative safety. Chemical composition of such medicines is usually complex, they may be represented by heteropolymers or mixtures containing peptides, polysaccharides, and other compounds which are endogenous and/or rapidly metabolised in a living organism. Conventional, chromatography-based approaches to evaluation of such medicines are often not applicable. Pharmacokinetics of medicinal products of natural origin may be studied by methods based on assessment of biological action and pharmacodynamic properties of such medicines, which involves determination of biological marker (biomarker) levels. The aim of the study was to summarise the accumulated experimental data on the use of biomarkers in pharmacokinetics studies as illustrated by a few medicinal products of natural origin. Material and methods. The authors studied fucoidan from Fucus vesiculosus, as well as a complex of bioactive compounds and a glycopeptide—both isolated from gonads of green sea urchins (Strongylocentrotus droebachiensis). In vitro/ex vivo experiments were used to establish correlation between the concentrations of the test mixtures and the activity/concentration of potential biomarkers. Experiments showing the biomarker concentration in plasma or serum (in vitro) and whole blood (ex vivo) before and after spiking with the studied products were performed in order to assess specificity, calibration (linear) range of the biomarker response, and its native concentration. The analytical procedures were based on the chromogenic (optical) anti-factor Xa activity (AXA) assay, and determination of dipeptidyl peptidase 4 and lactate dehydrogenase activity by kinetic analysis with spectrophotometric detection of enzymatic reaction products. Results. The analysis of the results of studies of a number of natural products (fucoidan from Fucus vesiculosus; a complex of bioactive compounds isolated from gonads of green sea urchins S. droebachiensis; a glycopeptide isolated from internal organs of S. droebachiensis) demonstrated the feasibility of using biomarkers in pharmacokinetics studies of such products. This approach allowed for accurate calculation of pharmacokinetic parameters.Conclusion. The discussed approach may be used for various biological models and is an effective means of studying compounds that are difficult or impossible to detect by conventional bioassays in pharmacokinetics and bioequivalence studies.
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