Take Care with Repeated Drug Administration via the Intraperitoneal Route

Chance findings from our laboratory over the winter of 2016-2017 demonstrated that repeated administration of investigational compounds formulated in 0.5% methylcellulose (MC) by the intraperitoneal (IP) route to mice could cause significant histological damage to peripheral organs, such as the liver, spleen and kidneys. Because MC is a very common formulation vehicle that is often used to deliver investigational compounds for the treatment of epilepsy, it was possible that this organ damage could also lead to significant changes in the phenotype of the mouse model of epilepsy itself.

Our recent publication in the Journal of Pharmacology and Experimental Therapeutics sought to definitively establish whether repeated IP administration of 0.5% MC to mice could alter the fidelity of an epilepsy model. While there was no significant change in the severity or stability of chronic kindled seizures, we did detect a considerable amount of histopathology within multiple peripheral organs. Care should thus be taken when electing to administer investigational agents repeated by the IP route as this could lead to significant organ damage that, if not properly controlled, could be inadvertently attributed to the investigational compound.

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