title: The pharmacokinetic profiles of dexamethasone and methylprednisolone concentration in perilymph and plasma following systemic and local administration.
abstract: CONCLUSIONS
  Both methylprednisolone (MTH) and dexamethasone (DEX) could successfully and effectively penetrate the round window membrane (RWM) into perilymph. RWM topical application and otocyst infusion with MTH and DEX result in high perilymph drug concentrations and low plasma levels. An intratympanic administration schedule for DEX or MTH could be carried out twice daily.
  
  
  OBJECTIVE
  To explore the pharmacokinetics of DEX and MTH in the inner ear fluids and plasma following systemic and local administration.
  
  
  METHODS
  Three routes of administration of steroids were used in guinea pigs: intracardial injection, otocyst infusion and RWM topical application by granule gelfoam soaked with steroids. Samples of blood or perilymph of the scala tympani were collected at 1-6 h after administration. High-performance liquid chromatography was used to assay concentrations of steroids.
  
  
  RESULTS
  Both the topical application and infusion administration resulted in a significantly higher concentration of steroids in perilymph than intracardial injection. The level of steroids in the perilymph reached a peak at 1-2 h after dosing, and this was maintained at a relatively high level for several hours. The intracardial injection with steroids yielded very low perilymph levels at all sampling times after administration.
authors.affiliation: Department of Otorhinolaryngology-Head & Neck surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Hou
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Shun-Guo
authors.initials: SG
authors.lastname: Zhang
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D006321:Heart; D007267:Injections; D008657:Metabolic Clearance Rate / Q000502:physiology; D008775:Methylprednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010037:Otolithic Membrane / Q000378:metabolism; D010498:Perilymph / Q000378:metabolism*; D012405:Round Window, Ear / Q000378:metabolism
chemical_list: D003907:Dexamethasone; D008775:Methylprednisolone