OBJECTIVETo investigate the distribution and pharmacokinetics of dexamethasone of different concentrations in the inner ears of SD rats after intratympanic injection.

METHODSTotally 144 adult SD rats were anaesthetized and dexamethasone sodium phosphate of different concentrations (5 mg/ml, 10 mg/ml, 20 mg/ml) was injected into the tympanums. The rats were sacrificed at various postinjection survival times (5 min, 10 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h), and every 4 rats were included into each group. Then after a series of processes the inner ear tissue was cryostat sectioned. The distribution of dexamethasone was evaluated using immunofluorescence with semiquantitative analysis. Immunofluorescence was also used in another 4 normal SD rats to detect the distribution of Glucocorticoid receptor (GR) in the inner ear.

RESULTSDexamethasone was observed initially 15 min after local drug administration and 30 min to its peak level. The highest concentration of dexamethasone labeling was seen in the spiral ligament, organ of Corti and spiral ganglion, which paralleled the distribution of GR. The tissue concentration of 10 mg/ml and 20 mg/ml groups was higher than 5 mg/ml every corresponding time point, and the lasting time was also prolonged from 48 hours to 72 hours.

CONCLUSIONSDexamethasone can enter into the cochlear tissue quickly after transtympanic injection, and its distribution accords nearly exactly with that of GR. Increase of the concentration of dexamethasone results in higher tissue distribution and longer lasting time.