Toxicokinetics – Methodological Approaches

O. Pozharitskaya, PhD in pharmacy, deputy director, A. Shikov, PhD in pharmacy, DrSci, deputy director, V. Makarov, PhD in medicine, professor, director Saint Petersburg Institute of Pharmacy Leningradskiy region, Vsevolozhskiy district, Kuzmolovskiy, st. Zavodskaya, 3. b. 245, 188663, Russia Е-mail: info@doclinika.ru

Abstract

The article discusses the importance of integration of pharmacokinetics in toxicity testing. This will be helpful in interpretation of the results of toxicological studies and ensure the development of a rational study design. The term “toxicokinetics” in the context of the development of medicines means obtaining pharmacokinetic data either as an integral component when conducting preclinical toxicity studies or in specially designed studies to determine systemic concentration. The data obtained can also be used for interpretation of the results of toxicological date and their relevance in terms of clinical safety issues. The current practice of drug development requires toxicological study from the very early stage of the search for possible candidates for drugs. Toxicokinetic studies conducted at the early stage are necessary to establish a more accurate goal in the development process. The toxicokinetic section is an integral part of the preclinical testing program and the information obtained is intended to increase the value of the toxicological data obtained, both from the point of view of understanding toxicity studies, and in comparison with clinical data as part of a person’s risk and safety assessment. Due to the inclusion of toxicity and the comparison of preclinical and clinical docie, the main focus is on the interpretation of toxicity data, and not on the characterization of the main pharmacokinetic parameters of the substance under study. The main aim of the toxicokinetic study is to determine the systemic concentrations achieved in animals and to identify their relationship with the dose level and the period of the toxicity study. In addition, when conducting toxicokinetic studies, secondary aims are: to determine the relationship between the concentrations achieved in toxicity studies and the results of toxicological studies, and to assess the compliance of the obtained data with the parameters of clinical safety; confirm the selection of the type and mode of therapy data preclinical toxicity studies; obtain information that, together with the results of toxicity studies, will allow the design of subsequent preclinical toxicity studies to be developed. Toxicokinetics also helps to select the dosing regimen and the dosing interval of drugs / chemicals necessary for successful therapy and / or experimental studies.

References

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