Results from the simulationsa
Simulation results depicting the effect of decreased blood flow on tumor topotecan concentrations after infusing the drug intraperitoneally.
Blood Flow to Tumor (ml/min/g) | 0.006 | 0.015 | 0.03 | 0.06 |
| Intraperitoneal concentration (ng/ml) | 2697 | 2693 | 2691 | 2690 |
| Blood concentration (ng/ml) | 27 | 27.1 | 27.1 | 27.2 |
| Concentration in tumor layer A (ng/ml) | 574 | 293 | 171 | 102 |
| Concentration in tumor layer B (ng/ml) | 145 | 55.1 | 35.3 | 29.4 |
| Concentration in tumor layer C (ng/ml) | 54.7 | 30.3 | 27.6 | 27.2 |
| Concentration in tumor layer D (ng/ml) | 34.6 | 27.5 | 27.2 | 27.2 |
| Concentration in tumor layer E (ng/ml) | 30.1 | 27.1 | 27.1 | 27.2 |
| Tumor homogenate concentration (ng/g) | 334 | 166 | 100 | 65 |
↵ a All simulations were performed using the hybrid physiologically based pharmacokinetic model and were based on an animal weighing 25 g. Topotecan was infused either intraperitoneally or intravenously at the dose of 15 mg/kg over the period of 72 h. To simulate the effect of antiangiogenic therapy on tumor blood perfusion, different simulations were performed with varying values of tumor blood flow. For the purpose of simulation, the normal tumor blood flow value of 0.06 ml/min/g was reduced by 50, 75, and 90%. All simulations were performed with ADAPT-II software (University of Southern California).