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Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice
Published on: October 27, 2014
Paclitaxel-induced peripheral neuropathy in male rats attenuated by calmangafodipir, a superoxide dismutase mimetic
Takehiro Kawashiri1, Kohei Mori1, Haruna Ishida1
1Department of Clinical Pharmacy and Pharmaceutical Care, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Abstract:
Paclitaxel induces peripheral neuropathy, which is considered a dose-limiting factor. However, appropriate prophylactic agents are currently unavailable. We investigated the prophylactic effects of calmangafodipir, a superoxide dismutase mimetic, on paclitaxel-induced peripheral neuropathy using a male rat model. Repeated administration of paclitaxel (6 mg/kg, intraperitoneal, once weekly for 4 weeks) resulted in mechanical allodynia in the von Frey test and axonal degeneration in the sciatic nerve. Conversely, calmangafodipir (1-10 mg/kg, intravenous, thrice weekly for 4 weeks) prevented mechanical allodynia and axonal degeneration induced by paclitaxel. These results suggest that calmangafodipir may inhibit paclitaxel-induced peripheral neuropathy.

