喹诺酮类药物的角膜和巩膜通透性——一项药代动力学研究。

Corneal and scleral permeability of quinolones--a pharmacokinetics study.

作者信息

Tai Ming-Cheng, Lu Da-Wen, Chiang Chiao-Hsi

机构信息

Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.

出版信息

J Ocul Pharmacol Ther. 2003 Dec;19(6):547-54. doi: 10.1089/108076803322660468.

DOI:10.1089/108076803322660468

PMID:14733712

Abstract

PURPOSE

To investigate the corneal and scleral permeability of nalidixic acid and synthesized fluoroquinolones and their in vivo pharmacokinetics in rabbits.

METHODS

The corneal and scleral permeability coefficients of ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were determined in rabbits using high performance liquid chromatography (HPLC). The aqueous humor levels of norfloxacin and ciprofloxacin were measured separately by topical instillation of 0.3% solutions of the two drugs onto rabbit eyes.

RESULTS

Nalidixic acid had a higher corneal permeability coefficient (17.3 +/- 3.56 x 10(-6) cm/second) than all other drugs tested (p < 0.01). Corneal permeability coefficients in rabbits among ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were not significantly different (p > 0.1). Comparing the corneal and scleral permeability coefficients, only values for nalidixic acid were not significantly different (17.35 +/- 3.56 x l0(-6) cm/second versus 22.69 +/- 5.19 x 10(-6) cm/second, p > 0.05), while all other drugs had scleral permeability coefficients 8 to 10 times greater than corneal permeability coefficients. The mean aqueous humor concentration of norfloxacin and ciprofloxacin at 60 minutes to 180 minutes after instillation was around 0.3 microg/mL, a value higher than MIC90 of most bacteria.

摘要

目的

研究萘啶酸及合成氟喹诺酮类药物在兔体内的角膜和巩膜通透性及其体内药代动力学。

方法

采用高效液相色谱法（HPLC）测定环丙沙星、诺氟沙星、西诺沙星、依诺沙星和氧氟沙星在兔体内的角膜和巩膜通透系数。通过将0.3%的这两种药物溶液分别局部滴入兔眼，来分别测量诺氟沙星和环丙沙星的房水浓度。

结果

萘啶酸的角膜通透系数（17.3±3.56×10⁻⁶厘米/秒）高于所有其他受试药物（p<0.01）。环丙沙星、诺氟沙星、西诺沙星、依诺沙星和氧氟沙星在兔体内的角膜通透系数无显著差异（p>0.1）。比较角膜和巩膜通透系数，只有萘啶酸的值无显著差异（17.35±3.56×10⁻⁶厘米/秒对22.69±5.19×10⁻⁶厘米/秒，p>0.05），而所有其他药物的巩膜通透系数比角膜通透系数大8至10倍。滴入后60分钟至180分钟，诺氟沙星和环丙沙星的房水平均浓度约为0.3微克/毫升，该值高于大多数细菌的MIC90。