Prediction of volume of distribution in preclinical species and humans: application of simplified physiologically based algorithms
Creators: name: Nigade, Prashant B.
name: Jayasagar Gundu
name: K. Sreedhara Pai
name: Nemmani, Kumar V. S.
name: Talwar, Rashmi
Publisher: name: Taylor & Francis
Year: 2018
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Physiology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: FOS: Chemical sciences
subject: 69999 Biological Sciences not elsewhere classified
subject: 80699 Information Systems not elsewhere classified
subject: FOS: Computer and information sciences
subject: FOS: Computer and information sciences
subject: Developmental Biology
subject: Plant Biology
subject: Computational Biology

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