[Permeability of the round window membrane for prednisolone-21-hydrogen succinate. Prednisolone content of the perilymph after local administration vs. systemic injection].
OBJECTIVE
Prednisolone is the drug of first choice for the treatment of cochleovestibular disorders, such as sudden hearing loss. Because of the known side effects, the efficient drug levels to be achieved within inner ear fluids are limited by intravenous administration. The aim of the study was to determine the concentration in the perilymph of prednisolone-21-hydrogen succinate applied into the round window niche in comparison to the concentration after intraperitoneal application.


METHODS
Application of prednisolone-21-hydrogen succinate (5 mg in 0.1 ml) on the round window membrane was performed after sedation under microscopic view directly into the round window niche of the guinea pig. In order to compare the results, perilymph samples after systemic application of 60 mg/kg body weight prednisolone were used. The time between application and taking specimens of perilymph from the cochlea varied. Specimens of perilymph were obtained after 15, 20, 80, 180, 330, and 960 min (10 specimens in each group, n = 60) by dissecting the cochlea and opening the apex cochleae. Levels of prednisolone-21-hydrogen succinate in perilymph were measured by isocratic high-pressure liquid chromatography (HPLC).


RESULTS
The highest levels of prednisolone-21-hydrogen succinate were found after 180 min: 952.3 mg/l (95% confidence interval: 382.7). After 960 min the level was 18.72 mg/l (95% confidence interval: 16.9). In the group with systemic application, the levels measured were below 14.71 mg/l (95% confidence interval: 7.05).


CONCLUSIONS
The results demonstrate that high levels of prednisolone-21-hydrogen succinate in perilymph are achievable by local application of a single dose into the round window niche. After application of 5 mg, the levels of prednisolone are measurable up to 16 h.
Bachmann
G
G
Klinik und Poliklinik für Hals-, Nasen-, Ohrenheilkunde, Universität zu Köln.
Su
J
J
Zumegen
C
C
Wittekindt
C
C
Michel
O
O
D000287:Administration, Topical; D000818:Animals; D001682:Biological Availability; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D008657:Metabolic Clearance Rate / Q000502:physiology; D010498:Perilymph / Q000378:metabolism*; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D012405:Round Window, Ear / Q000378:metabolism*
D011239:Prednisolone; C021322:prednisolone hemisuccinate