Lack of peripheral neuropathy in Beagle dogs after 53 weeks oral administration of thalidomide capsules
| Autor: | M Brockman, D Allen, M Morgan, Mark G. Evans, J Ehrhart, Steve D. Thomas, Steve K. Teo, D Stirling |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Health Toxicology and Mutagenesis Neural Conduction Action Potentials Administration Oral Capsules Leprostatic Agents Sural nerve 010501 environmental sciences Toxicology 030226 pharmacology & pharmacy 01 natural sciences Beagle 03 medical and health sciences Dogs 0302 clinical medicine Sural Nerve Oral administration Evoked Potentials Somatosensory Toxicity Tests medicine Animals Tibial nerve Adverse effect 0105 earth and related environmental sciences Dose-Response Relationship Drug business.industry Peripheral Nervous System Diseases General Medicine medicine.disease Thalidomide Surgery medicine.anatomical_structure Peripheral neuropathy Peripheral nervous system Anesthesia Female business medicine.drug |
| Zdroj: | Human & Experimental Toxicology. 19:615-622 |
| ISSN: | 1477-0903 0960-3271 |
| DOI: | 10.1191/096032700673027800 |
| Popis: | 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. Thali-domide 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. |
| Databáze: | OpenAIRE |
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