The pharmacokinetic profiles of dexamethasone and methylprednisolone concentration in perilymph and plasma following systemic and local administration.
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.
Yang
Jun
J
Department of Otorhinolaryngology-Head & Neck surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Wu
Hao
H
Zhang
Ping
P
Hou
Dong-Ming
DM
Chen
Jie
J
Zhang
Shun-Guo
SG
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
D003907:Dexamethasone; D008775:Methylprednisolone