Comparison of open and closed abdomen techniques for the delivery of intraperitoneal pemetrexed using a murine model.

Abstract

BACKGROUND AND OBJECTIVES: Pemetrexed is an appealing agent to use for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the optimal method of pemetrexed delivery still remains undefined. Using a murine model, we compared the use of open and closed abdomen techniques on the absorption of intraperitoneal (IP) pemetrexed in different compartments. METHODS: Eleven Sprague-Dawley rats were submitted to a fixed dose of IP pemetrexed (1000&#x2009;mg/m) at a perfusion temperature of 40&#xb0;C during 25&#x2009;min according to two techniques: open and closed. At the end of perfusion, samples in different compartments were harvested and the concentrations of pemetrexed were measured by high performance liquid chromatography. RESULTS: Absorption of IP pemetrexed in portal and systemic blood was significantly higher using the open compared to the closed abdomen technique (93.17 vs 52.50&#x2009;&#xb5;g/mL, P&#x2009;<&#x2009;0.001) and (76.26 vs 51.65&#x2009;&#xb5;g/mL, P&#x2009;<&#x2009;0.001), respectively. No difference was found between the two techniques on the peritoneal tissue concentration of pemetrexed (18.07 vs 19.17&#x2009;&#xb5;g/g, P&#x2009;=&#x2009;0.51). CONCLUSION: Peritoneal absorption of pemetrexed is not modified by the use of either technique. However, systemic concentrations of pemetrexed increased using the open technique, suggesting it could increase systemic toxicity.