Certain benzimidazoles, fenbendazole and mebendazole, have demonstrated in vitro efficacy against glioma cells due to inhibition of tubulin polymerization and disruption of microtubule formation. Fenbendazole produces these effects at a mean inhibitory concentration (IC50) of 150 ng/ml, which might be an initial target for therapeutic CSF concentrations. Our study aimed to describe the time course of fenbendazole in plasma and CSF after oral administration to dogs. Doses were designed to target a CSF concentration approaching 150 ng/ml. Fenbendazole was detected in canine plasma and CSF using high performance liquid chromatography; the limit of detection was 10 ng/ml and 5 ng/ml, respectively. Fenbendazole administered to two dogs at 50 mg/kg was not detectable. Dogs were subsequently treated with 100 mg/kg (n = 4) and then 200 mg/kg (n = 2 due to adverse effect), resulting in an average peak plasma concentration (ng/ml) of 131.5 and 133.4, respectively. CSF concentrations were detectable in less than 25 % of the samples. The highest CSF concentration (at 200 mg/kg) was 21.19 ng/ml at 360 min. However, dogs given 200 mg/kg had acute onset of hematochezia, suggesting doses this high may not be clinically appropriate. This study demonstrates that plasma fenbendazole concentrations increased with dose, but CSF concentrations were well below the target of 150 ng/ml even at 200 mg/kg. Relevance of this target concentration to efficacy for treatment of gliomas remains to be determined. Future studies might focus on a more potent benzimidazole such as mebendazole, for which the in vitro IC50 is lower.
Auburn University College of Veterinary Medicine
Dr. Brenna is a third year Neurology & Neurosurgery resident at Auburn University. She completed her Bachelor's in Neuroscience at Washington State University in 2009 and continued on at the WSU College of Veterinary Medicine to receive her DVM in 2013. During her time at the WSU CVM, she was a part of the Research Scholar's program where her research focused on CSF biomarkers of neural injury. Dr. Brenna completed a Small Animal Medicine and Surgery internship in Seattle, and a Neurology/Neurosurgery specialty internship in Dallas, prior to beginning her Neurology and Neurosurgery residency at Auburn University in 2015. Her current research investigates the antineoplastic properties of fenbendazoles in canine gliomas.
Thursday, June 14
1:30 PM – 1:45 PM
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