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)

Abstract

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
JournalXenobiotica
Volume49
Issue number5
DOIs
Publication statusPublished - 04-05-2019

Fingerprint

Tissue
Organ Size
Tissue Distribution
Individuality
Rodentia
Muscle
Rats
Dogs
Blood
Lipids
Muscles
Lung

All Science Journal Classification (ASJC) codes

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

Cite this

Nigade, Prashant B. ; Gundu, Jayasagar ; Pai, K. Sreedhara ; Nemmani, Kumar V.S. ; Talwar, Rashmi. / Prediction of volume of distribution in preclinical species and humans : application of simplified physiologically based algorithms. In: Xenobiotica. 2019 ; Vol. 49, No. 5. pp. 528-539.
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Prediction of volume of distribution in preclinical species and humans : application of simplified physiologically based algorithms. / Nigade, Prashant B.; Gundu, Jayasagar; Pai, K. Sreedhara; Nemmani, Kumar V.S.; Talwar, Rashmi.

In: Xenobiotica, Vol. 49, No. 5, 04.05.2019, p. 528-539.

Research output: Contribution to journalArticle

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