This review summarized some approaches to establishing interspecies allometric relationships for pharmacokinetic parameters of drugs defined by statistical analysis of individual time -concentration profiles of substances in blood of several animal species. The presented interspecies allometric relationships for basic pharmacokinetic parameters could be used in preclinical pharmacokinetics investigations.Preclinical pharmacokinetic studies of new drugs in animals are used to extrapolate the pharmacokinetic parameters to man, to select drug doses for phase I clinical trials, and to evaluate the safety for humans of new drug candidates [1,2]. The experimental pharmacological methodical approach that calculates the distribution of a candidate drug in human blood and organs from experimental data obtained in laboratory animal tests is called interspecies scaling of pharmacokinetic data. Work on interspecies scaling of pharmacokinetic data developed rapidly since the 1960s and is associated with researchers such as L. B. Mellet [3], R. L. Dedrick [4 -6], H. Boxenbaum [7 -12], and J. Mordenti [13 -15]. Their studies were a logical continuation of research on the physiological similarity of biological species that started already in the 1930s [16 -18].The methodology of interspecies scaling of pharmacokinetic data is currently developing in two relatively independent directions that differ in the pharmacokinetic models used to determine the drug pharmacokinetic parameters and employed interspecies scaling methods [19 -29]. The allometric method of pharmacokinetic data scaling is elaborated in the most detail. It is commonly used for interspecies analysis of drugs with different pharmacokinetics [19 -26].The present review analyzed the procedures for obtaining interspecies allometric functions for the principal drug pharmacokinetic parameters to be determined by statistical processing of individual drug concentration distributions in several animal species. Basic principles of allometric interspecies scaling of pharmacokinetic dataThe allometric method received its name because of the non-linear equations for the interspecies dependences of mammalian physiological parameters and drug pharmacokinetic parameters. The numerical parameters of the allometric equation are determined by statistical processing of experimental data obtained in tests on several biological species. Hence, another name for the method is statistical.The drug pharmacokinetics should be linear in the studied dose range and the metabolic pathways in man and animals used for the calculations should be similar in order to use this method. However, examples were reported where the allometric method was applied successfully and the metabolic pathways in animals and man differed, e.g., during an analysis of interspecies differences in theophylline distribution [30]. Much literature data demonstrated that the allometric equations were in general suitable for predicting pharmacokinetic parameters in man using animal data [11, 15, 22, 26, 31 -37].The allometri...

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Цель работы — выявление сезонных колебаний в составе и морфологии крови интактных крыс. Анализировали морфометрические показатели крови 36 клинически здоровых половозрелых крыс самцов в разные сезоны (весна, лето и осень) при помощи АПК «МЕКОС». Выявленные сезонные колебания в пределах установленных референтных значений необходимо учитывать при проведении доклинических исследований лекарственных препаратов на предмет их эффективности и безопасности.

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