Sebbag Lionel, Kirner Nicolette S, Allbaugh Rachel A, Reis Alysha, Mochel Jonathan P
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
Department of Biomedical Sciences, SMART Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
Front Vet Sci. 2019 Dec 19;6:457. doi: 10.3389/fvets.2019.00457. eCollection 2019.
The study aimed to determine the impact of drop size on tear film pharmacokinetics and assess important physiological parameters associated with ocular drug delivery in dogs. Two separate experiments were conducted in eight healthy Beagle dogs: (i) Instillation of one drop (35 μl) or two drops (70 μl) of 1% fluorescein solution in each eye followed by tear collections with capillary tubes from 0 to 180 min; (ii) Instillation of 10 to 100 μl of 0.1% fluorescein in each eye followed by external photography with blue excitation filter (to capture periocular spillage of fluorescein) and tear collections from 1 to 20 min (to capture tear turnover rate; TTR). Fluorescein concentrations were measured in tear samples with a fluorophotometer. The TTR was estimated based upon non-linear mixed-effects analysis of fluorescein decay curves. Tear film pharmacokinetics were not superior with instillation of two drops vs. one drop based on tear film concentrations, residual tear fluorescence, and area under the fluorescein-time curves ( ≥ 0.163). Reflex TTR varied from 20.2 to 30.5%/min and did not differ significantly ( = 0.935) among volumes instilled (10-100 μl). The volumetric capacity of the canine palpebral fissure (31.3 ± 8.9 μl) was positively correlated with the palpebral fissure length ( = 0.023). Excess solution was spilled over the periocular skin in a volume-dependent manner, predominantly in the lower eyelid, medial canthus and lateral canthus. In sum, a single drop is sufficient for topical administration in dogs. Any excess is lost predominantly by spillage over the periocular skin as well as accelerated nasolacrimal drainage.
该研究旨在确定液滴大小对泪膜药代动力学的影响，并评估与犬眼药物递送相关的重要生理参数。在八只健康的比格犬身上进行了两项独立实验：（i）每只眼睛滴入一滴（35μl）或两滴（70μl）1%荧光素溶液，随后用毛细管在0至180分钟内收集眼泪；（ii）每只眼睛滴入10至100μl 0.1%荧光素，随后用蓝色激发滤光片进行外部摄影（以捕捉荧光素在眼周的溢出），并在1至20分钟内收集眼泪（以捕捉泪液周转率；TTR）。用荧光光度计测量泪液样本中的荧光素浓度。基于荧光素衰减曲线的非线性混合效应分析估算泪液周转率。基于泪膜浓度、残留泪液荧光和荧光素-时间曲线下面积（≥0.163），两滴给药与一滴给药相比，泪膜药代动力学并无优势。反射性泪液周转率在20.2%至30.5%/分钟之间变化，在所滴入的体积（10 - 100μl）之间无显著差异（P = 0.935）。犬睑裂的容积（31.3±8.9μl）与睑裂长度呈正相关（P = 0.023）。过量溶液以体积依赖的方式溢出到眼周皮肤，主要在下眼睑、内眦和外眦。总之，单滴给药足以用于犬的局部给药。任何过量的药物主要通过溢出到眼周皮肤以及加速鼻泪管引流而流失。
