Pharmacokinetic and pharmacodynamic optimization of intraperitoneal chemotherapy

Intraperitoneal drug administration has been utilized to increase chemotherapeutic exposure to tumors confined to the peritoneal cavity, such as those found in ovarian, gastric, cole-rectal and mesotheliomal cancers. Extensive pre-clinical and clinical experimentation has been conducted to assess the pharmacokinetic and therapeutic benefits of this mode of therapy. Pharmacokinetic studies have shown that the barrier function of the peritoneal membrane may be utilized to produce large, favorable concentration gradients between peritoneal perfusate and blood. However, most clinical studies so far have demonstrated minimal increases in drug efficacy or decreases in drug toxicities from intraperitoneal drug therapy alone. This paper reviews the application of adjunctive therapies that have been rationally conceived to optimize intraperitoneal drug therapy through the alteration of antineoplastic pharmacokinetics and pharmacodynamics.