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Distribution

Dist inputs

The tissue-to-plasma (TP) ratios are computed using drug physicochemical parameters mainly log P, log D, pKa, protein binding, blood-to-plasma ratio and other parameters such as tissue/organ neutral and acidic phospholipid content, hematopoietic content etc.
If logD is not available, please leave the value at 0.0 and the following equation is used to calculate the same:1


log D = 1.15 ⨯ log P - 1.35[ 1 ]

There are various methods in the literature to compute the TP ratios and only two methods are currently available on Teoreler - Rodgers & Rowland 2-4and Poulin and Theil. 1
For PBPK modelling, the user is provided with the option to choose a volume of distribution method. An optional input to enter a scalar value is provided under 'Optional inputs' tab named 'Distribution scalar'. This scalar would change all the predicted TP ratios by the entered scalar value. By default the factor is 1 meaning that it is not scaled. The volume of distribution in the simulated output table is reported in L/kg.


References

  1. Poulin P, Theil FP. Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution. J Pharm Sci. 2002 Jan;91(1):129-56. https://doi.org/10.1002/jps.10005
  2. Rodgers T, Rowland M. Physiologically based pharmacokinetic modelling 2: Predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions. Journal of Pharmaceutical Sciences. 2006;95(6):1238-57. https://doi.org/10.1002/jps.20502
  3. Rodgers T, Leahy D, Rowland M. Physiologically Based Pharmacokinetic Modeling 1: Predicting the Tissue Distribution of Moderate-to-Strong Bases. Journal of Pharmaceutical Sciences. 2005;94(6):1259-76. https://doi.org/10.1002/jps.20322
  4. Rodgers T, Rowland M. Mechanistic Approaches to Volume of Distribution Predictions: Understanding the Processes. Pharmaceutical Research. 2007;24(5):918-33. https://doi.org/10.1007/s11095-006-9210-3.