Pharmacokinetics and the effect of heat on intraperitoneal pemetrexed using a murine model

Abstract Background Pemetrexed is a systemic chemotherapeutic agent used in the treatment of malignant mesothelioma. This drug represents a potentially promising intraperitoneal (IP) agent to use for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal mesothelioma. Howev...

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Bibliographic Details
Published in:Surgical oncology 2016-12, Vol.25 (4), p.435-440
Main Authors: Badrudin, David, Perrault-Mercier, Camille, Bouchard-Fortier, Antoine, Hubert, Julien, Leblond, François A, Sideris, Lucas, Dubé, Pierre
Format: Article
Language:English
Subjects:
Abdomen
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacokinetics
Blood
Catheters
Chemotherapy
Cytoreductive surgery
Heat
Hematology, Oncology and Palliative Medicine
HIPEC
Hot Temperature
Injections, Intraperitoneal
Male
Mesothelioma
Models, Animal
Mortality
Pemetrexed
Pemetrexed - administration & dosage
Pemetrexed - pharmacokinetics
Peritoneal mesothelioma
Peritoneum - drug effects
Peritoneum - metabolism
Pharmacokinetics
Rats
Rats, Sprague-Dawley
Rodents
Surgery
Temperature
Tissue Distribution
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Summary:Abstract Background Pemetrexed is a systemic chemotherapeutic agent used in the treatment of malignant mesothelioma. This drug represents a potentially promising intraperitoneal (IP) agent to use for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal mesothelioma. However, this has yet to be supported by preclinical studies. Therefore, we aimed to study the effect of pemetrexed dose and perfusion temperature on the resultant pemetrexed concentration in 3 different compartments (systemic circulation, portal circulation and peritoneal tissues) using a murine model. Methods Under general anesthesia, 29 Sprague-Dawley rats were submitted to 3 different doses of IP pemetrexed (500, 1000 and 1500 mg/m2 ) combined with 3 different perfusion temperatures (37, 40 and 43 °C) for a total duration of 25 min. At the end of perfusion, samples in different compartments (systemic circulation, portal circulation and peritoneum) were harvested and concentrations of pemetrexed were measured using high performance liquid chromatography. Results With increasing dose of IP pemetrexed, higher concentrations were measured in the 3 compartments tested. In peritoneal cells, the difference between IP doses of 500 and 1000 mg/m2 (2.03 vs. 19.17 μg/g, p  
ISSN:0960-7404
1879-3320
DOI:10.1016/j.suronc.2016.05.014