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

Abstract
Thalidomide (Thalomid) is approved for use in the US to treat complications from leprosy. Peripheral neuropathy is a dose-limiting adverse event in humans. As part of a nonrodent regulatory toxicology study, Beagle dogs were fed orally via encapsulation for 53 weeks. A component of this study was to determine if the dogs developed peripheral neuropathy. Twenty-eight male and 28 female Beagle dogs approximately 8-10 months of age were used. They were dosed at 43, 200 or 1000 mg/kg for 53 weeks followed by a 4-week treatment-free recovery period. Nerve function was assessed by electrophysiological 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 and 58 weeks and histologic and ultrastructural evaluations were performed on the sural nerve. Thalidomide had no effect on sensory nerve conduction velocity, duration or amplitude of the action potential. At 27 weeks, mean sensory nerve action potential amplitude for females at 43 mg/kg was significantly greater than control but was not evident at 39 weeks. Mean duration of sensory nerve action potential seemed to increase with similar magnitude over time in all dose groups including controls. Histological and ultrastructural evaluation of sections of sural nerve did not identify treatment-induced differences between control and thalidomide-dosed animals after 26 and 53 weeks of treatment. Additionally, no differences were observed following a 5-week treatment-free period at week 58. In contrast to humans, Beagle dogs did not develop thalidomide-induced peripheral neuropathy under conditions of the study.
AuthorsS Teo, M Evans, J Ehrhart, M Brockman, D Allen, M Morgan, D Stirling, S Thomas
JournalHuman & experimental toxicology (Hum Exp Toxicol) Vol. 19 Issue 11 Pg. 615-22 (Nov 2000) ISSN: 0960-3271 [Print] England
PMID11211239 (Publication Type: Journal Article)
Chemical References
  • Capsules
  • Leprostatic Agents
  • Thalidomide
Topics
  • Action Potentials (drug effects, physiology)
  • Administration, Oral
  • Animals
  • Capsules
  • Dogs
  • Dose-Response Relationship, Drug
  • Evoked Potentials, Somatosensory (drug effects, physiology)
  • Female
  • Leprostatic Agents (administration & dosage, toxicity)
  • Male
  • Neural Conduction (drug effects, physiology)
  • Peripheral Nervous System Diseases (etiology, pathology, physiopathology)
  • Sural Nerve (drug effects, physiology, ultrastructure)
  • Thalidomide (administration & dosage, toxicity)
  • Toxicity Tests

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