Liu Hong-Jian, Dong Ming-Min, Chi Fang-Lu
Department of Otorhinolaryngology, Eye and ENT Hospital of Fudan University, Shanghai City, China.
ORL J Otorhinolaryngol Relat Spec. 2006;68(2):93-8. doi: 10.1159/000091210. Epub 2006 Jan 27.
To study the dexamethasone pharmacokinetics in the inner ear perilymph of guinea pigs using high-pressure liquid chromatography.
Sixty-five guinea pigs were divided into three groups. In the first group, the drug application protocol used an intra-abdominal dose of 0.5% dexamethasone 4 mg x kg(-1). In the second group, an intratympanic application dose of 0.5% dexamethasone 150 microl was used. The third group was the control group. The concentrations of dexamethasone in inner ear perilymph were determined by high-pressure liquid chromatography.
The perilymph concentration-time curves of dexamethasone conformed to a one-compartment open model after an intra-abdominal application. The Cmax was 0.927 +/- 0.008 mg x l(-1), the Tmax 1.47 +/- 0.04 h, the T(1/2K) 2.92 +/- 0.056 h, the AUC 5.533 +/- 0.05 mg x h x l(-1), the T(1/2Ka) 0.47 +/- 0.024 h. After an intratympanic application, the perilymph concentration-time curves of dexamethasone also conformed to a one-compartment open model. The Cmax was 0.201 +/- 0.006 mg x l(-1), the Tmax 0.117 +/- 0.06 h, the AUC 0.868 +/- 0.004 mg x h x l(-1), the T(1/2K) 2.918 +/- 0.089 h, the T(1/2Ka) 0.161 +/- 0.009 h. Compared to the intra-abdominal application, the intratympanic application resulted in similar levels of inner ear perilymph drug concentrations in 30 min.
Dexamethasone can penetrate the blood-labyrinthine barrier after intra-abdominal application. Dexamethasone can enter into perilymph after intratympanic application. Under the condition of the study, the intratympanic application resulted in a similar level of inner ear perilymph drug concentrations compared to the intra-abdominal application in 30 min.
采用高效液相色谱法研究地塞米松在豚鼠内耳外淋巴中的药代动力学。
65只豚鼠分为三组。第一组，腹腔给药剂量为0.5%地塞米松4mg·kg⁻¹。第二组，鼓室内给药剂量为0.5%地塞米松150μl。第三组为对照组。采用高效液相色谱法测定内耳外淋巴中地塞米松的浓度。
腹腔给药后，地塞米松的外淋巴浓度 - 时间曲线符合一室开放模型。Cmax为0.927±0.008mg·l⁻¹，Tmax为1.47±0.04h，T(1/2K)为2.92±0.056h，AUC为5.533±0.05mg·h·l⁻¹，T(1/2Ka)为0.47±0.024h。鼓室内给药后，地塞米松的外淋巴浓度 - 时间曲线也符合一室开放模型。Cmax为0.201±0.006mg·l⁻¹，Tmax为0.117±0.06h，AUC为0.868±0.004mg·h·l⁻¹，T(1/2K)为2.918±0.089h，T(1/2Ka)为0.161±0.009h。与腹腔给药相比，鼓室内给药在30分钟时内耳外淋巴药物浓度水平相似。
腹腔给药后地塞米松可穿透血迷路屏障。鼓室内给药后地塞米松可进入外淋巴。在本研究条件下，鼓室内给药在30分钟时内耳外淋巴药物浓度水平与腹腔给药相似。
