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目的:分析不同方式鼓室内给药后豚鼠耳蜗外淋巴液中地塞米松(DEX)代谢动力学特征,为临床选择鼓室内给药方式提供实验依据。方法:采用浸满DEX溶液明胶海绵颗粒置于圆窗龛内和鼓室内灌注两种鼓室内给药方式,采集给药后1～6h豚鼠鼓阶外淋巴液,应用高效液相色谱仪分别检测其中的DEX浓度。结果:相同浓度(10g/L)的DEX溶液经明胶海绵圆窗龛给药后外淋巴液中的DEX浓度1h时最高,DEX生物半衰期t1/2为2.37h。鼓室内灌注给药后外淋巴液中的DEX浓度1h20min时最高,DEX生物半衰期为t1/2为2.26h。除1h20min、1h40min和2h外,两种方式鼓室内给药后外淋巴液中DEX的浓度相比差异均有统计学意义(均P<0.05)。结论:明胶海绵颗粒圆窗龛给药和鼓室内灌注给药两种方式鼓室内给药后DEX均能有效地经圆窗膜渗透进入外淋巴液,大部分时间明胶海绵颗粒圆窗龛给药外淋巴液中的DEX浓度高于鼓室内灌注给药。明胶海绵圆窗龛给药的生物半衰期较长。
OBJECTIVE: To analyze the pharmacokinetics of dexamethasone (DEX) in the guinea pig cochlear extralymphatic after different modes of administration in the tympanic cavity, and to provide experimental basis for clinical selection of intratympanic administration mode. Methods: Gelatin sponge particles impregnated with DEX solution were placed in circular window niches and infused into the tympanic cavity. Two types of intra-tympanic administration were used. Guinea pigs’ extra-amphillary lymph were collected 1 ~ 6 h after drug administration, and were measured by high performance liquid chromatography Which DEX concentration. Results: The DEX concentration of peritoneal lymphatic fluid of DEX solution with the same concentration (10g / L) was highest after 1h of gelatin sponge round window niche, and the biological half-life of DEX was 2.37h. After intratracheal instillation, the concentration of DEX in perilymph was highest at 1h20min, and the biological half-life of DEX was 2.26h at t1 / 2. Except for 1h20min, 1h40min and 2h, there were significant differences in DEX concentration between the two methods after intratympanic administration (all P <0.05). CONCLUSION: DEX can penetrate into the perilymph effectively through the round window membrane after administration of gelatin sponge round window niche and intraluminal perfusion, and the round window niche of gelatin sponge particles can be administered most of the time The DEX concentration in the perilymph is higher than that in the intratympanic perfusion. The biological half-life of gelatin sponge round window niche is longer.