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

Prashant B. Nigade, Jayasagar Gundu, K. Sreedhara Pai, Kumar V.S. Nemmani, Rashmi Talwar

Research output: Contribution to journalArticle

1 Citation (Scopus)


The present study was aimed at developing simplified physiologically based semi-mechanistic algorithms to predict V ss and interspecies scaling factors to predict tissue-K p s which require minimum input parameters, diminish the computing complexity and have better predictability. V ss of 86 structurally diverse compounds in preclinical species and 27 compounds in humans were predicted using only lung- and muscle-K p 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-K p s were predicted for 34 compounds using the newly developed interspecies scaling factors. The predicted-to-experimental V ss values for all the 113 compounds was 1.3 ± 0.9 with 83% values being within a factor of two. The tissue-K p s in rat, dog and human were predicted using experimental tissue-K p data in rodents and interspecies scaling factors and here also, 83% of tissue-K p s 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-K p s, in which required input parameters as well as computing complexity have been noticeably reduced.

Original languageEnglish
Pages (from-to)528-539
Number of pages12
Issue number5
Publication statusPublished - 04-05-2019


All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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