2-Year animal carcinogenicity results for crisaborole, a novel phosphodiesterase 4 inhibitor for atopic dermatitis.
J Dermatol Sci
; 87(2): 116-122, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28416366
ABSTRACT
BACKGROUND:
Crisaborole is a novel, topical nonsteroidal, anti-inflammatory, phosphodiesterase 4 (PDE4) inhibitor for the treatment of mild to moderate atopic dermatitis.OBJECTIVE:
As part of a nonclinical safety testing program, these 2-year studies tested the carcinogenic potential of crisaborole.METHODS:
Crisaborole ointment, 2%, 5%, or 7%, was applied once daily topically to mice, and crisaborole was administered orally to rats at doses of 30, 100, or 300mg/kg/day for up to 104 weeks. Systemic exposure to crisaborole and its metabolites, moribundity/death, clinical signs, and tumor formation were assessed in each study.RESULTS:
Crisaborole treatment was not tumorigenic in mice at any of the doses administered and did not increase the incidence of neoplastic or nonneoplastic microscopic lesions compared with controls. Oral administration of crisaborole at the high dose (300mg/kg/day) to female rats increased the incidence of treatment-related benign granular cell tumors in the distal reproductive tract (uterus with cervix and vagina) but did not cause moribundity/death.CONCLUSION:
Crisaborole was well tolerated and not tumorigenic in mice. It was not tumorigenic in male rats at 300mg/kg/day at exposures that were 3× the human area under the concentration-time curve (AUC24) and was nontumorigenic in female rats at 100mg/kg/day at exposures that were 1× the human AUC24.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Compostos de Boro
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Anti-Inflamatórios não Esteroides
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Compostos Bicíclicos Heterocíclicos com Pontes
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Inibidores da Fosfodiesterase 4
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Carcinogênese
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Neoplasias dos Genitais Femininos
Tipo de estudo:
Incidence_studies
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Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article