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

• Published in: Journal of surgical oncology Vol. 117; no. 6; pp. 1318 - 1322
• Main Authors: Badrudin, David, Sideris, Lucas, Perrault‐Mercier, Camille, Hubert, Julien, Leblond, François A., Dubé, Pierre
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-05-2018
• Subjects: Abdomen; Cancer surgery; experimental study; HIPEC; pemetrexed; HIPEC; experimental study; pemetrexed
• ISSN: 0022-4790; 1096-9098
• DOI: 10.1002/jso.24960

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 mg/m2) at a perfusion temperature of 40°C during 25 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 µg/mL, P < 0.001) and (76.26 vs 51.65 µg/mL, P < 0.001), respectively. No difference was found between the two techniques on the peritoneal tissue concentration of pemetrexed (18.07 vs 19.17 µg/g, P = 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.