Lack of peripheral neuropathy in Beagle dogs after 53 weeks oral administration of thalidomide capsules

Thalidomide (Thalomid(R)) is approved for use in the US to treat complicati ons from leprosy. Peripheral neuropathy is a dose-limiting adverse event in humans. As part of a nonrodent regulatory toxicology study, Beagle dogs we re fed orally via encapsulation for 53 weeks. A component of this study was to determine if the dogs developed peripheral neuropathy. Twenty-eight mal e and 28 female Beagle dogs approximately 8-10 months of age were used. The y were dosed at 43, 200 or 1000 mg/kg for 53 weeks followed by a 4-week tre atment-free recovery period. Nerve function was assessed by electrophysiolo gical measurements of the tibial nerve prior to dosing and at weeks 13, 27, 38 and 51. Representative dogs from each group were sacrificed at 26, 53 a nd 58 weeks and histologic and ultrastructural evaluations were performed o n the sural nerve. Thalidomide had no effect on sensory nerve conduction ve locity, duration or amplitude of the action potential. At 27 weeks, mean se nsory nerve action potential amplitude for females at 43 mg/kg was signific antly greater than control but was not evident at 39 weeks. Mean duration o f sensory nerve action potential seemed to increase with similar magnitude over time in all dose groups including controls. Histological and ultrastru ctural evaluation of sections of sural nerve did not identify treatment-ind uced differences between control and thalidomide-dosed animals after 26 and 53 weeks of treatment. Additionally, no differences were observed followin g a 5-week treatment-free period at week 58. In contrast to humans, Beagle dogs did not develop thalidomide-induced peripheral neuropathy under condit ions of the study.