Effect of hyperthermia on the pharmacokinetic profile of oxaliplatin administered by intraperitoneal route in rats

14535 Background: Whereas in vitro studies have demonstrated that hyperthermia enhances the cytotoxicity and tissue penetration of oxaliplatin, in vivo studies conducted so far have failed to document clearly such effect in the context of heated intraperitoneal chemotherapy. The purpose of this study is to assess the effect of heat on the pharmacokinetic profile of oxaliplatin administered intraperitonealy in rats. Methods: Under general anesthesia, 25 Sprague-Dawly rats of 258 g (235–440 g) were submitted to 3 different doses of intraperitoneal oxaliplatin (460, 920 and 1840 mg/m2) at 3 different temperatures of perfusion (37, 40 and 43°C) during 25 minutes. At the end of perfusion, samples in different compartments were harvested for dosage of oxaliplatin concentration: 2 ml of perfusate, 1 ml of portal blood, 1 ml of systemic blood, 100 mm3 of parietal peritoneum and 100 mm3 of mesentery. Dosage of oxaliplatin was performed by high performance liquid chromatography. Results: We observed a linear and p...