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Preclinical safety evaluation of amphotericin A21: A novel antifungal
Author(s) -
OrtegaBlake Ivan,
FernándezZertuche Mario,
Regla Ignacio,
SánchezPeña Walfred,
GómezSolis Antonieta,
JaimesChavez Paola,
GalvánHernández Arturo,
TovarGarduño Erika,
RodríguezFragoso Lourdes
Publication year - 2021
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13592
Subject(s) - antifungal , amphotericin b , pharmacology , medicine , intensive care medicine , echinocandins , dermatology , caspofungin
Abstract Safety studies are essential in drug development. This study evaluates the safety of Amphotericin A21 (AmB‐A21), a derivative of amphotericin B with antifungal therapeutic potential. We performed a chronic toxicity study, a targeted organ study and a dermal irritation test. To evaluate chronic toxicity, 18 male adult rats were treated orally with AmB‐21 (2 mg/kg) for 26 weeks. The effects on body‐weight and animal health were measured, and haematological, clinical chemistry and histopathological tests were conducted on various organs. In the target organ toxicity study, male adult rats received a daily oral dose of AmB‐21 (2 mg/kg) for 6 and 17 weeks; testicle histology and testosterone levels were then evaluated. For the dermal irritation study, AmB‐21 (200 and 1000 mg/kg) was placed on the skin of adult male rabbits; macroscopic and microscopic studies, as well as haematological and clinical chemistry tests were then conducted. The chronic toxicity study revealed that AmB‐21 caused testicle damage, and the testicle‐targeted study showed structural alterations and changes in testosterone levels at 17 weeks. However, these alterations were no longer observed 8 weeks after discontinuation of treatment, and the testes showed very similar characteristics to those in the control group. The dermal irritation study showed skin thickening and reddening in rabbits treated with 2000 mg of AmB‐A21 after 14 days of exposure. This same group also showed changes in liver enzymes, renal parameters and platelet levels. Based on our results, we consider AmB‐21 to be a potential candidate for safe, long‐term antifungal treatment given its reduced side effects.