The effect of beta-cyclodextrin complexation on the bioavailability and hepatotoxicity of clotrimazole.
Pharmazie
; 62(10): 756-9, 2007 Oct.
Article
em En
| MEDLINE
| ID: mdl-18236780
ABSTRACT
Clotrimazole, a poorly water-soluble antimycotic agent, is a promising therapeutic agent for various diseases including cancer and sickle cell anemia. The oral bioavailability and hepatic toxicity of clotrimazole were compared with its beta-cyclodextrin inclusion form which was prepared by the spray-drying method. The inclusion complex gave significantly higher initial plasma concentrations, Cmax and AUC than did clotrimazole alone, indicating that the drug from the inclusion compound could be more easily absorbed in rats. Furthermore, mice treated with the inclusion compound showed significantly higher GOT/GPT values compared to clotrimazole alone. The inclusion compound also induced hypertrophy of hepatic cells by fat accumulation and disappearance of hepatic sinusoids, indications of pathological changes of liver, suggesting that the inclusion compound could induce more severe tissue damage in the liver than clotrimazole alone. Thus, hepatotoxicity of clotrimazole seems to be correlated with the enhanced oral bioavailability by inclusion complexation. Our results suggest that, in the development of a novel oral product, appearance or enhancement of hepatic toxicity must be considered along with oral bioavailability.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Clotrimazol
/
Beta-Ciclodextrinas
/
Doença Hepática Induzida por Substâncias e Drogas
/
Antifúngicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pharmazie
Assunto da revista:
FARMACIA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Coréia do Sul