Background: Because heat can improve the activity of selected drugs when administered heated in the peritoneal cavity in the treatment of peritoneal carcinomatosis from colorectal origin, there is a great interest to evaluate new cytotoxic agents in this context. The purpose of this study is to assess the effect of heat on the pharmacokinetic profi le of Raltitrexed administered intraperitoneally in rats.
Materiel/Methods: Rats #1 to #40 have been submitted to different doses of intraperitoneal Raltitrexed (2, 4, and 8 mg/m[sup]2[/sup]) at different perfusion temperatures (37, 40 and 43°C). After 25 minutes of perfusion, peritoneal fl uid, portal and systemic blood were harvested and prepared for dosage of Raltitrexed. Rats #41 to #50 have been submitted to 8 mg/m[sup]2[/sup] of intraperitoneal Raltitrexed (37 and 43°C) during 25 minutes. Then, a segment of small bowel and a section of parietal peritoneum were harvested and prepared for intracellular dosage of Raltitrexed. Results: The dose of Raltitrexed administered is a determinant of its concentration in peritoneal perfusate,
in portal vein blood and in systemic blood (p

Keywords: Quinazolines - administration & dosage, Thiophenes - administration & dosage, Antimetabolites, Antineoplastic - pharmacokinetics, Body Temperature, Heating, Injections, Intraperitoneal, Quinazolines - pharmacokinetics, Thiophenes - pharmacokinetics