Some aspects of drug toxicokinetics in preclinical studies (literature review)

Toxicokinetic studies are a key aspect of preclinical drug safety studies. Regulatory documents describe methodological approaches to the toxicokinetic study, but do not answer many questions that arise during their planning.

The purpose of this work was the analysis of literature data, domestic and foreign methodological documents related to the preclinical study of drugs toxicokinetic, own experience in conducting such studies to propose possible designs for experiments on the study of toxicokinetic in concomitant studies and in studies with the formation of satellite groups.

The study materials were regulatory documents, literature sources, and guidelines for the preclinical study of toxicokinetics of drugs in the public domain (including, according to the PubMed, Web of Science, RISC (eLibrary.ru), Google scholar electronic databases), which were subjected to further general scientific analysis and generalization.

The toxicokinetic data as part of the drug registration dossier are necessary to establish the relationship between the detected toxicity and the administered dose of the drug, are important for planning clinical studies, contributing to the determination of threshold values of the substance in blood plasma to assess early exposure to humans. The features of planning and experimental toxicokinetic study in various formats are considered, designs of such studies are proposed.

A review of the literature data, regulatory documents, and experimental experience related to the study of toxicokinetics, which is an important element of drug development, was carried out.

Authors’contribution:
Karlina M.V. – concept of research, analysis of domestic and foreign methodological documents, preparation of the text;
Kosman V.M. – discussion of data, integration of materials from their own experience, additions to the text;
Makarova М.N. – critical revision of the manuscript;
Makarov V.G. – approval of the final version of the article.
All co-authors – responsibility for the integrity of all parts of the article.

Conflict of interests. The authors declare no conflict of interest.

Funding. The study had no sponsorship.

Received: February 02, 2025 / Revised: March 12, 2025 / Accepted: July 14, 2025 / Published: August 29, 2025

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