Pharmacokinetics and disposition of CS-8958, a long-acting prodrug of the novel neuraminidase inhibitor laninamivir in rats.
Xenobiotica
; 40(3): 207-16, 2010 Mar.
Article
en En
| MEDLINE
| ID: mdl-20146556
ABSTRACT
CS-8958, a prodrug of laninamivir (R-125489), is currently under development as an inhaled anti-influenza drug. In this study, the pharmacokinetics and disposition of CS-8958 were characterized in rats. After intratracheal administration of 14C-CS-8958, radioactivity was retained over long periods in the target tissues (trachea and lung) as its active metabolite R-125489 - 19.12% of the dose was retained in the lung at 24 h. After intratracheal administration of CS-8958, plasma R-125489 concentration was slowly eliminated, and its half-life (14.1 h) was considerably longer than that after intravenous administration of R-125489. The radioactivity of intratracheally administered 14C-CS-8958 was mainly excreted into the urine (67.5% of dose), and this excretion lasted over long periods. R-125489 accounted for most of the urinary radioactivity recovered after 24 h. These results demonstrated that CS-8958 administered intratracheally to rats was converted/hydrolysed to R-125489 in the target tissues, and that the R-125489 was slowly excreted into the urine via an absorption rate-limiting process. Such distinctive pharmacokinetics attributed to the slow release of R-125489 suggests the potential for a long-acting anti-influenza drug.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Profármacos
/
Inhibidores Enzimáticos
/
Zanamivir
/
Neuraminidasa
Límite:
Animals
Idioma:
En
Revista:
Xenobiotica
Año:
2010
Tipo del documento:
Article
País de afiliación:
Japón