ABSTRACT

This chapter provides an overview of approaches that may enhance tissue penetration of intraperitoneal chemotherapy. It describes the use of pharmacodynamic modeling as a powerful tool to relate tissue drug concentrations to the exerted effects such as apoptosis. Pharmacokinetic–pharmacodynamic (PKPD) modeling is recognized as a promising tool for quantitative decision making in oncology. PKPD models that are constructed based on an in-depth understanding of the relationships between drug concentration and treatment outcome are a valuable tool to optimize/individualize treatment regimens. The two main physical mechanisms of drug transport into tumor tissue are diffusion and convection. The efficacy of the drug ultimately depends on the intracellular concentrations that result from active and passive transport across the cell membrane. Since tissue drug transport of most currently used chemotherapeutic agents is driven largely by passive diffusion, and thus by a concentration gradient, any increase in the peritoneal drug concentration is likely to enhance peritoneal tumor exposure.