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Dose Selection in Preclinical Studies: Cross-Species Dose Conversion
Author(s) -
E.V. Shekunova,
М. А. Ковалева,
М.Н. Макарова,
В. Г. Макаров
Publication year - 2020
Publication title -
vedomosti naučnogo centra èkspertizy sredstv medicinskogo primeneniâ
Language(s) - English
Resource type - Journals
eISSN - 2619-1172
pISSN - 1991-2919
DOI - 10.30895/1991-2919-2020-10-1-19-28
Subject(s) - pharmacokinetics , pharmacodynamics , selection (genetic algorithm) , pharmacology , medicine , clinical trial , drug , clinical pharmacology , computational biology , medical physics , computer science , biology , machine learning , pathology
One of the major obstacles to effective translational medicine is the challenge of translating animal research results into clinical studies. Scientific literature mainly addresses the selection of the drug dose at initiation of clinical trials (Phase 1). Appropriate selection of doses is also essential for preclinical toxicology and pharmacology studies. Some basic principles that are used when translating dosages from animal models to humans are applicable to selection and justification of doses when planning and conducting preclinical studies. The paper provides an overview of the main methods that can be used for selection and justification of animal doses in preclinical studies, e.g. cross-species dose conversion using body surface area scaling. It summarises situations when doses may be directly converted based on body weight. The paper gives special attention to cross-species dose translation according to pharmacokinetic data. There is no one-size-fits-all approach to cross-species translation; dose conversion must be scientifically justified taking into consideration all information available on the test drug, i.e. its chemical structure, intended route of administration, pharmacokinetic parameters, preclinical and clinical data on pharmacodynamics, and inter-species differences in pharmacokinetics and pharmacodynamics.

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