Table 10:
Sensitivity analysis for parameters of dibenzo[def,p]chrysene (DBC) physiologically based pharmacokinetic (PBPK) model. Sensitivity coefficients were categorized as “Low” (absolute value of sensitivity coefficient < 0.1), “Medium” (absolute value of sensitivity coefficient > 0. 1 and < 0.5), and “High” (absolute value of sensitivity coefficient > 0.5).
| Parameter | Symbol | Sensitivity Category | Sensitivity Category | ||
|---|---|---|---|---|---|
| Mouse Model | Human Model | ||||
| DBC Concentration in Blood | DBC-Diol Concentration in Blood | DBC Concentration in Blood | DBC-Diol Concentration in Blood | ||
| Metabolism | |||||
| Maximum rate of reaction for DBC metabolism | vmlpc | High | High | High | High |
| Michaelis constant for DBC metabolism | kmlp | High | High | High | High |
| First order rate for Phase 1 metabolism of DBC-Diol | cllmlc | Low | High | Low | High |
| Maximum rate of reaction for Phase II metabolism of DBC-Diol | vml2mlc | Low | Low | Low | Medium |
| Michaelis constant for Phase II metabolism of DBC-Diol | km 12ml | Low | Low | Low | Medium |
| Absorption | |||||
| Absorption rate from stomach to liver | kas | High | High | Low | Low |
| Absorption rate from intestines to liver | ksi | High | High | High | High |
| Gastric emptying rate | kai | High | High | High | High |
| Compartment Volumes | |||||
| Arterial blood | vac | Low | Low | Low | Low |
| Venous blood | wc | High | High | High | High |
| Fat | vfc | High | High | Medium | High |
| Liver | vie | High | High | High | High |
| Lung | vlngc | Low | Low | Low | Low |
| Rapidly Perfused | vrc | Medium | Medium | Medium | Medium |
| Slowly Perfused | vsc | Medium | High | High | High |
| Blood Flows | |||||
| Fat | qfc | High | High | Medium | Medium |
| Liver | qlc | High | High | High | High |
| Rapidly Perfused | qrc | Medium | Medium | Medium | Medium |
| Alowly Perfused | qsc | Medium | Medium | Medium | Medium |
| Partition Coefficients (DBC) | |||||
| Fat | pfp | High | High | Medium | Low |
| Liver | pip | High | High | High | High |
| Slowly perfused | psp | High | Medium | High | High |
| Rapidly perfused | prp | Medium | Low | Medium | Medium |
| Lung | plngp | Low | Low | Low | Low |
| Partition Coefficients (DBC-Diol) | |||||
| Fat | pfml | Low | High | Low | Low |
| Liver | plml | Low | High | Low | High |
| Slowly perfused | psml | Low | Medium | Low | High |
| Rapidly perfused | prml | Low | Medium | Low | Medium |
| Lung | plngml | Low | Low | Low | Low |
| Other | |||||
| Fractional oral absorption | per_abs | High | High | High | High |
| Fractional metabolism factor | fracl | Low | High | Low | High |
| Fractional protein binding (DBC) | fbp | High | Medium | High | High |
| Fractional protein binding (DBC-Diol) | fbml | Low | High | Low | High |