Prediction of volume of distribution in preclinical species and humans: application of simplified physiologically based algorithms

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Prashant B NigadeRashmi Talwar

Abstract

The present study was aimed at developing simplified physiologically based semi-mechanistic algorithms to predict Vss and interspecies scaling factors to predict tissue-Kps which require minimum input parameters, diminish the computing complexity and have better predictability. Vss of 86 structurally diverse compounds in preclinical species and 27 compounds in humans were predicted using only lung- and muscle-Kp as inputs. Interspecies scaling factor (s) were developed based on fold-differences in individual tissue lipid contents, relative organ blood flow: relative organ weight ratio between two species. Tissue-Kps were predicted for 34 compounds using the newly developed interspecies scaling factors. The predicted-to-experimental Vss values for all the 113 compounds was 1.3 ± 0.9 with 83% values being within a factor of two. The tissue-Kps in rat, dog and human were predicted using experimental tissue-Kp data in rodents and interspecies scaling factors and here also, 83% of tissue-Kps were within two-fold of the experimental values. In conclusion, simplified physiologically based algorithms have been developed to predict both volume of distribution and tissue-Kps, in which required input parameters as well as computing comple...Continue Reading

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Citations

Jun 20, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Carl PeterssonHugues Dolgos
Nov 27, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Neha MuradAndrew D Weber

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