PHARMACOKINETIC AND PHARMACODYNAMIC OPTIMIZATION OF INTRAPERITONEAL CHEMOTHERAPY

Intraperitoneal drug administration has been utilized to increase chem otherapeutic exposure to tumors confined to the peritoneal cavity, suc h as those found in ovarian, gastric, cole-rectal and mesotheliomal ca ncers. Extensive pre-clinical and clinical experimentation has been co nducted 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 blo od. However, most clinical studies so far have demonstrated minimal in creases in drug efficacy or decreases in drug toxicities from intraper itoneal drug therapy alone. This paper reviews the application of adju nctive therapies that have been rationally conceived to optimize intra peritoneal drug therapy through the alteration of antineoplastic pharm acokinetics and pharmacodynamics.