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/