title: Pharmacokinetics of dexamethasone solution following intratympanic injection in guinea pig and sheep.
abstract: 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.
authors.affiliation: Otonomy Inc., San Diego, CA 92121, USA.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.forename: Rayne
authors.initials: R
authors.lastname: Fernandez
authors.forename: Luis
authors.initials: L
authors.lastname: Dellamary
authors.forename: Anne
authors.initials: A
authors.lastname: Harrop
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ye
authors.forename: Jay
authors.initials: J
authors.lastname: Lichter
authors.forename: David
authors.initials: D
authors.lastname: Lau
authors.forename: Carl
authors.initials: C
authors.lastname: Lebel
authors.forename: Fabrice
authors.initials: F
authors.lastname: Piu
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000493:pharmacokinetics*; D005260:Female; D006168:Guinea Pigs; D007267:Injections; D010498:Perilymph; D012756:Sheep; D014432:Tympanic Membrane
chemical_list: D003907:Dexamethasone