Hehl E M, Beck R, Luthard K, Guthoff R, Drewelow B
Institute of Experimental and Clinical Pharmacology and Toxicology, Deparment of Clinical Pharmacology, University of Rostock, Germany.
Eur J Clin Pharmacol. 1999 Jun;55(4):317-23. doi: 10.1007/s002280050635.
In order to improve the penetration of topically applied drugs in ophthalmology, the suitability of hydrophilic contact lenses (Acuvue, Vistacon, power -1.0 D) as a drug delivery system for antibiotics was tested. A prospective study was undertaken to determine the transcorneal penetration of five topically applied aminoglycosides and fluoroquinolones into the aqueous humour of patients.
Two hundred and sixty-five patients undergoing cataract extraction received 0.3% gentamicin, kanamycin, tobramycin, ciprofloxacin or ofloxacin solution by two different modes of administration: either as eye drops (nine drops every 15 min, starting 2 h prior to surgery) or by means of a drug delivery system (Acuvue contact lenses soaked for 1 h in eye drop solution without preservatives, 15 h prior to surgery). At the beginning of cataract extraction, 50-100 microl aqueous fluid was aspirated from the anterior chamber and immediately stored at -80 degrees C. Antibiotic concentrations were measured using fluorescence polarisation immunoassays (aminoglycosides) or high-performance liquid chromatography (fluoroquinolones).
After soaking for 1h in 0.3% eye drop solutions, Acuvue contact lenses released about 190-250 microg aminoglycoside and ofloxacin and 1000 microg ciprofloxacin. These amounts are considerably lower or in the same order of magnitude than obtained with application of eye drops (1350 microg). From the aminoglycosides tested, only gentamicin and tobramycin, but not kanamycin, were able to penetrate into the aqueous humour of patients. After the wearing of antibiotic-soaked lenses, mean aqueous humour concentrations were higher than after the use of eye drops. This difference reached significance in tobramycin (1.09 (1.30) microg x ml(-1) vs 0.49 (0.79) microg x ml(-1)), ciprofloxacin (1.23 (0.60) microg x ml(-1) vs 0.38 (0.33) microg x ml(-1)) and ofloxacin (5.55 (2.53) microg x ml(-1) vs 0.56 (0.37) microg x ml(-1)). The percentage of patients with aqueous humour concentration above the MIC90 of Staphylococcus epidermidis, the most common cause of postoperative endophthalmitis, was 92% and 100% after wearing ciprofloxacin- or ofloxacin-soaked lenses, respectively.
Gentamicin and tobramycin penetrated into the aqueous humour of patients, whereas kanamycin was not able to overcome the corneal barrier. Acuvue contact lenses soaked in 0.3% eye drop solutions can release sufficient amounts of gentamicin, ciprofloxacin and ofloxacin to produce bacteriostatic concentrations in the humor aquosus. Acuvue contact lenses can be recommended as a drug delivery system for fluoroquinolones.
为提高眼科局部应用药物的渗透性,测试亲水性隐形眼镜(Acuvue、Vistacon,屈光度-1.0 D)作为抗生素药物递送系统的适用性。开展一项前瞻性研究,以确定五种局部应用的氨基糖苷类和氟喹诺酮类药物经角膜向患者房水的渗透情况。
265例接受白内障摘除术的患者通过两种不同给药方式接受0.3%庆大霉素、卡那霉素、妥布霉素、环丙沙星或氧氟沙星溶液:要么滴眼(术前2小时开始,每15分钟9滴),要么通过药物递送系统(术前15小时将Acuvue隐形眼镜在无防腐剂的滴眼液中浸泡1小时)。在白内障摘除术开始时,从前房抽取50 - 100微升房水,立即储存在-80℃。使用荧光偏振免疫分析法(氨基糖苷类)或高效液相色谱法(氟喹诺酮类)测量抗生素浓度。
在0.3%滴眼液中浸泡1小时后,Acuvue隐形眼镜释放约190 - 250微克氨基糖苷类和氧氟沙星以及1000微克环丙沙星。这些量比滴眼给药(1350微克)得到的量低得多或处于相同数量级。在所测试的氨基糖苷类中,只有庆大霉素和妥布霉素能够渗透到患者房水中,而卡那霉素不能。佩戴浸泡抗生素的隐形眼镜后,房水平均浓度高于滴眼给药后。这种差异在妥布霉素(1.09(1.30)微克/毫升 vs 0.49(0.79)微克/毫升)、环丙沙星(1.23(0.60)微克/毫升 vs 0.38(0.33)微克/毫升)和氧氟沙星(5.55(2.53)微克/毫升 vs 0.56(0.37)微克/毫升)中具有统计学意义。房水浓度高于表皮葡萄球菌MIC90(术后眼内炎最常见病因)的患者百分比,在佩戴环丙沙星或氧氟沙星浸泡的隐形眼镜后分别为92%和100%。
庆大霉素和妥布霉素可渗透到患者房水中,而卡那霉素无法突破角膜屏障。在0.3%滴眼液中浸泡的Acuvue隐形眼镜可释放足够量的庆大霉素、环丙沙星和氧氟沙星,以在房水中产生抑菌浓度。Acuvue隐形眼镜可推荐作为氟喹诺酮类药物的递送系统。