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Pharmacokinetics of dexamethasone solution following intratympanic injection in guinea pig and sheep.
Wang, Xiaobo; Fernandez, Rayne; Dellamary, Luis; Harrop, Anne; Ye, Qiang; Lichter, Jay; Lau, David; Lebel, Carl; Piu, Fabrice.
Afiliación
  • Wang X; Otonomy Inc., San Diego, CA 92121, USA.
Audiol Neurootol ; 16(4): 233-41, 2011.
Article en En | MEDLINE | ID: mdl-20980743
Information on inner ear pharmacokinetics is limited in the literature, especially in large animals and in humans. A preliminary study was designed to explore the differences in inner ear exposure between guinea pigs and sheep following a single intratympanic injection of a 2% dexamethasone sodium phosphate solution. In both species, significant levels of dexamethasone were observed in the perilymph within 1 h, and decreasing by 50- to 100-fold within 12 h. Overall, the exposure to dexamethasone in the inner ear was significantly lower in sheep by 17- to 27-fold than in guinea pigs. Systemic and CNS exposure were minimal in both species as indicated by the low drug levels observed in plasma and CSF. Altogether, the preliminary evidence presented herein suggests the sheep as a practical and acceptable animal model to study the inner ear pharmacokinetics of drug candidates in large mammals and its potential towards extrapolation to human exposure.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Membrana Timpánica / Dexametasona Límite: Animals Idioma: En Revista: Audiol Neurootol Asunto de la revista: AUDIOLOGIA / PSICOFISIOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Membrana Timpánica / Dexametasona Límite: Animals Idioma: En Revista: Audiol Neurootol Asunto de la revista: AUDIOLOGIA / PSICOFISIOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza