豚鼠硫辛酸鼓室与静脉给药的内耳药代动力学比较

Comparison of the antioxidants lipoic acid pharmacokinetlcs in inner ear between intravenous and intratympanic administration in guinea pigs

目的比较静脉与鼓室给药，应用高效液相色谱技术（high．performanceliquidchromatography，HPLC）研究豚鼠外淋巴中的硫辛酸（1ipoicacid，LA）药代动力学特征，为临床选择给药方式和药物剂量提供参考。方法54只豚鼠随机分为2组，每组27只，分别经鼓室和静脉给予LA，给药质量浓度为100mg／ml。于给药后0．5、1、2、3、4、5、6、8、10h用HPLC检测豚鼠外淋巴中LA的质量浓度。结果豚鼠外淋巴中LA质量浓度在0．1～200μg／ml范围内线性关系良好（r2=0．9996），鼓室给药后外淋巴检测到最大药物质量浓度为171．7μg／ml，而静脉给药组为33．7μg／ml；静脉给药组动物的药物平均滞留时间为2．9h，鼓室给药组为3．7h；静脉给药组药物的半衰期为2．1h，鼓室给药组为1．8h。结论豚鼠LA静脉与鼓室给药后均能在外淋巴中检测到药物，但鼓室局部给药效果明显优于静脉全身给药。

Objective To study the pharmacokinetics of lipoic acid in guinea pig perilymph and to provide experimental evidence for clinical delivery methods and dose in order to compare of intravenous and intratympanic administration using high-performance liquid chromatography （HPLC）. Methods Fifty-four guinea pigs were randomly divided into two groups of intratympanic and intravenous administration, with 27 ones in each group, and the concentration of lipoic acid was 100 mg/ml. The concentration of lipoic acid in perilymph was detected respectively by HPLC at 0. 5, 1, 2, 3, 4, 5, 6, 8 and 10 h after administration. Results A well linear relation of concentration of lipoic acid in perilymph was shown when the concentration was detected from 0. 1 to 200 μg/ml （ r2 = 0. 9996 ） . The maximum of concentration of lipoic acid administrated via intratympanic was 171.7μg/ml, and via intravenous was 33.7 μg/ml; the MRT of intratympanic injection was 3. 7 h while intravenous injection was 2.9 h ; the half life（ tl/2 ） of the former was 1.8 h but the latter was 2. 1 h. Conclusions The drug concentration could both be detected via intravenous and intratympanic injection in perilymph of guinea pig, But the effect of local administration via intratympanic was obvious superior to systemic administration.