Aqueous Humor Concentrations of Topically Administered Caspofungin in Rabbits
Aqueous Humor Concentrations of Topically Administered Caspofungin in Rabbits
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DOI：
10.1159/000187627
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发表时间：
2008-12
影响因子：
2.1
通讯作者：
C. Vorwerk;S. Tuchen;F. Streit;L. Binder;W. Hofmüller;W. Behrens-Baumann
中科院分区：
文献类型：
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作者：
C. Vorwerk;S. Tuchen;F. Streit;L. Binder;W. Hofmüller;W. Behrens-Baumann
背景：棘白菌素卡泊芬净（CAS）是一种新型抗真菌药物，对所有念珠菌属均有体外杀菌活性，这是真菌性角膜炎最常见的原因。研究了局部给药后CAS通过角膜进入房水的渗透。方法：将浓度为7 mg/ml的CAS溶液应用于每只兔的角膜上。角膜上皮磨损后的药物施用在不同的时间间隔进行：单次施用，1和2 h后采集房水。此外，每30分钟连续应用CAS后，通过液相色谱串联质谱法分析1、2和5 h后的房水CAS浓度。结果：局部给药CAS无角膜上皮磨损导致在房水中检测不到药物量。然而，对于角膜擦伤，单次应用后，1小时后达到2.16 ± 1.57 μg/ml（n = 6）的水平，然后在2小时后降至1.76 ± 0.88 μg/ml（n = 2）。每30 min连续给药后，前房内CAS浓度分别为：1h后2.11 ± 1.09 μg/ml（n = 6），2 h后4.94 ± 1.80 μg/ml（n = 5），5 h后3.45 ± 2.11 μg/ml（n = 6）。结论：在房水中，治疗药物水平可以达到覆盖大多数真菌上皮磨损后的MIC。为了实现持续高水平的CAS作为角膜炎的有效抗真菌治疗，CAS应在去除角膜上皮后每30分钟局部施用。
Background: The echinocandin caspofungin (CAS) is a novel antifungal drug with fungicidal in vitro activity against all Candida spp., which are the most frequent cause of fungal keratitis. Penetration of CAS through the cornea into the aqueous humor after topical administration was investigated. Methods: A CAS solution with a concentration of 7 mg/ml was applied onto each rabbit’s cornea. Drug application after corneal epithelium abrasion was processed in different time intervals: single application with aqueous humor sampling after 1 and 2 h. In addition, after continuous application of CAS every 30 min, aqueous humor concentrations of CAS after 1, 2 and 5 h were analyzed by liquid-chromatography tandem mass spectrometry. Results: Topical administration of CAS without corneal epithelium abrasion resulted in no detectable amounts of the drug in the aqueous humor. However, with corneal abrasion, after a single application, levels of 2.16 ± 1.57 μg/ml (n = 6) were reached after 1 h and then decreased to 1.76 ± 0.88 μg/ml (n = 2) after 2 h. After serial application every 30 min, the following intracameral levels of CAS were detected: after 1 h, 2.11 ± 1.09 μg/ml (n = 6); after 2 h, 4.94 ± 1.80 μg/ml (n = 5), and after 5 h, 3.45 ± 2.11 μg/ml (n = 6). Conclusion: In the aqueous humor, therapeutic drug levels can be reached that cover the MICs of most fungi after epithelial abrasion. To achieve a sustained high level of CAS as an effective antifungal therapy for corneal keratitis, CAS should be administered topically every 30 min after removal of the corneal epithelium.