目的:为了揭示epinastine的渗透,抗过敏眼用剂,在兔眼睑皮肤上施用乳膏制剂后进入眼睑并分布到结膜。
方法:实验研究。
方法:用0.5%epinastine乳膏涂上刮毛的眼睑,然后制备眼睑组织切片,通过使用激光显微解剖组织和解吸电喷雾质谱成像(DESI-MSI)的液相色谱-串联质谱(LC-MS/MS)定量来确定epinastine的空间组织分布。此外,在眼睑应用0.5%epinastine乳膏或眼部滴注0.1%epinastine滴眼液后,使用LC-MS/MS测定睑结膜和球结膜中epinastine的浓度-时间曲线。
结果:激光显微切割结合LC-MS/MS分析在给药后0.5小时在眼睑最外层周围检测到高浓度的依匹斯汀,其逐渐扩散到眼睑深处,并在给药后8和24小时分布在结膜层中。在使用DESI-MSI获得的高空间分辨率图像中观察到类似的时间依赖性药物分布。结膜组织中的依匹斯汀浓度在施用0.5%依匹斯汀乳膏后4-8小时达到峰值,然后在施用后72小时内缓慢下降。相比之下,依匹斯汀滴眼液给药后,依匹斯汀浓度迅速达到峰值并急剧下降。
结论:将依皮斯汀乳膏应用于眼睑皮肤后,epinastine逐渐渗透到眼睑。该化合物在给药后8-24小时保留在结膜中,表明依皮斯汀乳膏是治疗过敏性结膜炎的有前途的长效制剂。
OBJECTIVE: To reveal the penetration of
epinastine, an anti-allergic ophthalmic agent, into the eyelid and its distribution to the conjunctiva after administration of a cream formulation on rabbit eyelid skin.
METHODS: Experimental study.
METHODS: Rabbits were treated with 0.5% epinastine cream on hair-shaved eyelids, followed by preparation of eyelid tissue slices to determine spatial tissue distribution of epinastine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification using laser-microdissected tissues and desorption electrospray ionization mass spectrometry imaging (DESI-MSI). In addition, following either eyelid application of 0.5% epinastine cream or ocular instillation of 0.1%
epinastine eye drops, concentration-time profiles of
epinastine in the palpebral conjunctiva and bulbar conjunctiva were determined using LC-MS/MS.
RESULTS: Laser microdissection coupled with LC-MS/MS analysis detected high concentrations of epinastine around the outermost layer of the eyelid at 0.5 h post-administration that gradually diffused deeper into the eyelid and was distributed in the conjunctival layer at 8 and 24 h post-administration. Similar time-dependent drug distribution was observed in high-spatial-resolution images obtained using DESI-MSI.
Epinastine concentrations in the conjunctival tissues peaked at 4-8 h after administration of 0.5%
epinastine cream and then decreased slowly over 72 h post-administration. In contrast,
epinastine concentrations peaked quickly and decreased sharply after
epinastine eye drop administration.
CONCLUSIONS: After the application of
epinastine cream to the eyelid skin,
epinastine gradually permeated the eyelid. The compound was retained in the conjunctiva for 8-24 h post-administration, indicating that epinastine cream is a promising long-acting formulation for treating allergic conjunctivitis.