Carcinogenicity Evaluation of Baclofen in TgrasH2 Mice
| Autor: | Bernard Palate, Guillaume Chevalier, Pramila Singh, Catherine Thirion-Delalande, Nicolas Aubert |
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| Rok vydání: | 2021 |
| Předmět: |
Agonist
Genetically modified mouse Baclofen Carcinogenicity Tests medicine.drug_class Transgene Alcohol abuse Mice Transgenic Pharmacology Toxicology Pathology and Forensic Medicine Mice chemistry.chemical_compound Oral administration medicine Animals Receptor Molecular Biology Carcinogen business.industry Cell Biology medicine.disease Rats Pharmaceutical Preparations chemistry Carcinogens business |
| Zdroj: | Toxicologic Pathology. 50:153-157 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/01926233211054767 |
| Popis: | Baclofen is a γ-aminobutyric acid-B receptor agonist used for control of spastic muscle activity and as a treatment for alcohol abuse. The review of the nonclinical database suggested a data gap for potential carcinogenicity following long-term use. Regulatory requirements for pharmaceutical safety testing of cancer-causing potential have historically included 2-year rodent studies in rats and mice. The availability of transgenic models with greater specificity and sensitivity to carcinogens provides safety testing alternatives that align with the 3Rs. The carcinogenicity of baclofen was evaluated in CB6F1-TgrasH2 transgenic mice following daily oral administration at 45, 90, and 180 mg/kg/d for 26 weeks, preceded by a 2-week drug-conditioning period. There were no treatment-related palpable masses or neoplastic findings, and survival rates were not affected by the baclofen treatment. In conclusion, baclofen was considered as noncarcinogenic in CB6F1-TgrasH2 mice, which is consistent with results previously obtained in a 2-year rat study. |
| Databáze: | OpenAIRE |
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