Intratympanic versus intravenous delivery of methylprednisolone to cochlear perilymph.
OBJECTIVE
To compare methylprednisolone concentrations in the perilymph of the human ear and in plasma after intratympanic (IT) or intravenous (IV) administration.


METHODS
Methylprednisolone concentrations in the perilymph of patients during cochlear implantation were compared after 3 dosing strategies of methylprednisolone solution for injection (40 mg/ml): 1) IT administration of up to 40 mg was injected into the middle ear through the external auditory canal via a 27-gauge needle passed through a small anterosuperior myringotomy; 2) IV administration of 1 mg/kg was given as a single injection over 30 seconds; 3) IV administration of 10 mg/kg was infused over 30 minutes. Perilymph (single sample, approximately 20 microL) was sampled using a needle passed through the round window membrane, from 0.5 to 3 hours after dosing. In most patients, simultaneous blood sampling was performed. Methylprednisolone concentrations were measured by high-performance liquid chromatography with a limit of quantification of 0.001 mg/L.


RESULTS
In 39 patients studied, 33 perilymph samples were suitable for measurement, along with 26 plasma samples. Median perilymph concentrations were 6.7 mg/L (n = 18; range, 0.2-89.4 mg/L) after IT administration, 0.053 mg/L (n = 8; range, 0-0.47 mg/L) after IV injection of 1 mg/kg, and 0.2 mg/L (n = 7; range, 0.067-3.1 mg/L) after IV infusion of 10 mg/kg. The median perilymph concentrations were 126-fold higher after the IT administration than after 1 mg/kg IV (p = 0.0003) and 33-fold higher than after 10 mg/kg IV infusion (p = 0.0045). Plasma concentrations after IT administration were 16-fold lower than after IV administration of 1 mg/kg (p = 0.0006), and 136-fold lower than after IV infusion of 10 mg/kg (p = 0.0006).


CONCLUSIONS
IT administration of methylprednisolone in humans results in much higher perilymph concentrations and much lower systemic concentrations than IV administration.
Department of Otolaryngology, Head and Neck Surgery, Christchurch Hospital, New Zealand. phil.bird@entdocs.co.nz
Philip A
PA
Bird
Evan J
EJ
Begg
Mei
M
Zhang
Allan T
AT
Keast
Daran P
DP
Murray
Thomas J
TJ
Balkany
D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003051:Cochlea; D019929:Cochlear Implantation; D004432:Ear, Middle; D005260:Female; D006801:Humans; D007223:Infant; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D010498:Perilymph / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D008775:Methylprednisolone