高黑色素粘合剂左氧氟沙星在兔子体内的全面药代动力学评估显示了局部滴眼液治疗后眼部疾病的潜力。

IF 5 2区 医学 Q1 OPHTHALMOLOGY
Sina Bahrpeyma, Paulina Jakubiak, Rubén Alvarez-Sánchez, Antonello Caruso, Monika Leuthardt, Claudia Senn, Eva M Del Amo, Arto Urtti
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引用次数: 0

摘要

目的:本研究旨在了解黑色素结合对通过不同给药途径给予高结合力模型药物后眼药代动力学的影响:方法:我们对色素兔和白化兔使用左氧氟沙星滴眼液(单次和多次)、玻璃体内注射和静脉注射。用液相色谱-质谱法(LC-MS/MS)分析了眼组织和血浆中的左氧氟沙星浓度,并计算了药代动力学参数:数据显示,左氧氟沙星在色素组织中富集并保留数周之久。静脉注射左氧氟沙星后,色素组织中的曲线下面积(AUC)值约为白化兔的 9 至 15 倍,但在局部滴用眼药水后,这一差异扩大到 255 至 951 倍。多次滴用眼药水会导致左氧氟沙星在色素组织中大量蓄积:AUC值是玻璃体内注射后的3至12倍。单次局部给药或静脉给药后的 AUC 值要低得多。在色素眼的神经视网膜中总是能观察到较高的药物浓度(0.1-35 µM);玻璃体内给药后的暴露量最高,然后是多剂量的局部滴注。对白化兔进行单次局部灌注和静脉注射后,玻璃体内的生物利用度分别为 0.009% 和 0.003%:黑色素结合可用于实现靶向给药并延长药物在眼部色素组织中的保留时间。局部多次给药实验的结果表明,滴眼液治疗可产生与玻璃体内给药相当的药物暴露和反应,甚至在视网膜色素上皮细胞和脉络膜中也是如此。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comprehensive Pharmacokinetic Evaluation of High Melanin Binder Levofloxacin in Rabbits Shows Potential of Topical Eye Drops for Posterior Segment Treatment.

Purpose: The purpose of this work was to understand the impact of melanin binding on ocular pharmacokinetics after administration of a high-binder model drug via different administration routes.

Methods: We applied levofloxacin to pigmented and albino rabbits as eye drops (single and multiple), as well as by intravitreal and intravenous injections. Ocular tissues and plasma were analyzed for levofloxacin concentrations with liquid chromatography-mass spectrometry (LC-MS/MS), and pharmacokinetic parameters were calculated.

Results: The data show enrichment of levofloxacin and weeks-long retention in pigmented tissues. Upon intravitreal injection, the area under the curve (AUC) values in pigmented tissues were about 9 to 15 times higher than the respective values in the albino rabbits, but this difference expanded to 255- to 951-fold following topical eye drop administration. Multiple dosing of eye drops led to substantial accumulation of levofloxacin in the pigmented tissues: AUC values were 3 to 12 times higher than after intravitreal injection. The AUCs were much lower after single topical or intravenous drug administrations. High drug levels (0.1-35 µM) were always observed in the neural retinas of pigmented eyes; the highest exposure was seen after intravitreal administration followed by multiple doses of topical drops. Single topical instillation and intravenous injections to the albino rabbits resulted in vitreal bioavailability values of 0.009% and 0.003%, respectively.

Conclusions: Melanin binding can be used to achieve targeted drug delivery and extended retention in pigmented ocular tissues. The results from topical multiple dosing experiments suggest that eye drop treatment may yield drug exposures and responses comparable to intravitreal delivery, even in the retinal pigment epithelium and choroid.

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来源期刊
CiteScore
6.90
自引率
4.50%
发文量
339
审稿时长
1 months
期刊介绍: Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.
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