Tox Volume
The tox compartment represents the tissue where on-target toxicity is being modeled. Tox Volume, \(V_{tox}\) is set to the volume within the tissue of interest that can be occupied by the drug. Most antibody-based or protein-based biotherapeutics are restricted to the extracellular space, so Tox Volume is set to represent the tissue interstitial volume.
Typical Values
The interstitial volume of tissues have been reported in literature and summarized as parameters in physiologically based pharmacokinetic (PBPK) models.
For example, Shah and Betts 2012 report values for interstitial volume of tissues:
| Tissue | Human (mL) | Mouse (mL) | Rat (mL) | Rhesus Monkey (mL) |
|---|---|---|---|---|
| Heart | 48.8 | 0.0217 | 0.146 | 4.05 |
| Lung | 300 | 0.0384 | 0.263 | 10.7 |
| Muscle | 3910 | 1.47 | 15.8 | 426 |
| Skin | 1125 | 1.66 | 16.5 | 223 |
| Adipose | 2289 | 0.337 | 5.63 | 26.3 |
| Bone | 1891 | 0.525 | 3.90 | 177 |
| Brain | 261 | 0.0873 | 0.410 | 16.9 |
| Kidney | 49.8 | 0.0788 | 0.361 | 4.09 |
| Liver | 429 | 0.385 | 2.56 | 37.4 |
| Small Intestine | 67.1 | 0.127 | 0.867 | 17.2 |
| Large Intestine | 95.3 | 0.0545 | 0.500 | 24.4 |
| Pancreas | 18 | 0.0169 | 0.173 | 2.17 |
| Thymus | 1.09 | 0.00153 | 0.0163 | 0.355 |
| Spleen | 44.3 | 0.0254 | 0.554 | 1.19 |
| Other | 831 | 0.0797 | 1.04 | 22.7 |
References
- Shah, Dhaval K., and Alison M. Betts. 2012. "Towards a Platform PBPK Model to Characterize the Plasma and Tissue Disposition of Monoclonal Antibodies in Preclinical Species and Human." Journal of Pharmacokinetics and Pharmacodynamics 39 (1): 67–86. https://pubmed.ncbi.nlm.nih.gov/22143261/