Table 4. Sensitivity of AUC0–7 for an antibody in mice to changes in Vv, V i and Q.
Tissue | Model-Predicted AUC0–7 Values | Experimentala | ||
Lit. | Meas. (naïve) | Meas. (+ B20) | (naïve) | |
blood | 82.5 | 93.0 | 93.1 | 122.2 |
liver | 18.1 | 9.37 | 9.64 | 20.7 |
kidneys | 18.7 | 17.8 | 17.1 | 21.8 |
spleen | 15.4 | 17.7 | 19.4 | 28.1 |
lungs | 36.7 | 49.5 | 50.2 | 33.1 |
heart | 17.4 | 17.6 | 19.3 | 24.3 |
muscle | 11.4 | 8.23 | 8.22 | 7.90 |
intestine | 7.03 | 3.77 | 4.71 | na |
bone | 7.58 | 8.55 | 8.56 | na |
Note: Comparison of model-predicted [13] and experimentally measured AUCs [%ID/g day], up to 7 days post-injection, calculated for an intact antibody in mice. All blood flow rates (Q), vascular (Vv) and interstitial (Vi) volumes were simultaneously changed from literature to measured values (see Tables 1 , 2 , 3 ) for these simulations, with the exception of Vi for kidneys, for which literature values were always used due to the effects of probe clearance. Measurement of Vv was accomplished using a previously reported indirect RBC labeling method [2].
Data for 125I-trastuzumab; reproduced with permissions [2].