Non-clinical toxicology evaluation of BIA 10-2474
| Autor: | Paul Moser, Patrício Soares-da-Silva, Klaus Weber, A. Wallace Hayes |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
BIA 10-2474 Pyridines business.industry Safety pharmacology Administration Oral 010501 environmental sciences Pharmacology Toxicology 01 natural sciences Amidohydrolases Rats Cyclic N-Oxides Clinical trial Mice 03 medical and health sciences Non clinical Fatty acid amide hydrolase Animals Humans Medicine Enzyme Inhibitors business 030304 developmental biology 0105 earth and related environmental sciences |
| Zdroj: | Critical Reviews in Toxicology. 51:65-75 |
| ISSN: | 1547-6898 1040-8444 |
| DOI: | 10.1080/10408444.2020.1867821 |
| Popis: | In 2016, one subject died and four were hospitalized with neurological symptoms during a clinical trial with the fatty acid amide hydrolase (FAAH) inhibitor BIA 10-2474. The present paper reviews the regulatory toxicology studies that were carried out to support the clinical trial application for BIA 10-2474. Animal studies complied with national and international standards including European regulatory guidelines (e.g. EEC Council Directive 75/318/EEC and subsequent amendments). The CNS effects seen in the rat and mouse appear to be common in rodents in such studies and do not in principle seem to be of the type to generate a signal. In the same way in non-human primates, insignificant alterations in the mesencephalon, and especially of the autonomic nervous system (Meissner's plexus in the bowel) in rodents and monkeys were observed in some animals treated with a high dose. Overall, these data, as well as the extensive additional data generated since the accident, support the conclusion that the tragic fatality that occurred during the clinical trial with BIA 10-2474 was unpredictable and that the mechanism responsible remains unknown, from a non-clinical toxicological perspective. |
| Databáze: | OpenAIRE |
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