Lu Hua-Yi, Wang Rui-Qing, Li Xin, Li Xu
Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin Province 130021, China.
The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
Evid Based Complement Alternat Med. 2020 Feb 27;2020:8120398. doi: 10.1155/2020/8120398. eCollection 2020.
The present study aimed to determine the pharmacokinetics and distribution of methylprednisolone sodium succinate (MPSS) and its metabolic product methylprednisolone (MP) in plasma and ocular tissues after periocular injection of MPSS in rabbit eyes. Forty-eight healthy New Zealand white rabbits were randomly divided into 12 groups, including the control group and 11 MPSS-treated groups sampling at different time points. Rabbits in the MPSS-treated groups underwent left eye periocular injection of MPSS (10 mg). The pharmacokinetics of MPSS and MP in plasma and ocular tissues (including aqueous humor, vitreous, iris, lens, sclera, optic nerve, and choroid and retina) were investigated by liquid chromatography tandem mass spectrometry (LC-MS/MS). After periocular injection, the time of maximum concentration ( ) of MPSS ranged from 0.25 h to 1 h in ocular tissues and was 0.25 h in plasma. of MP in ocular tissues ranged from 0.5 h to 6 h, and of MP in plasma was 0.5 h. The maximum concentration ( ) of MPSS and MP and the area under the curve (AUC ) in ocular tissues from high to low was sclera, optic nerve, choroid and retina, iris, and lens. Especially, the concentrations of MPSS and MP in the lens were much lower when compared with the other ocular tissues. After periocular administration, MPSS could be rapidly metabolized to its active constituent MP in the ocular tissues. Also, the MPSS can be delivered effectively into the posterior segment of the eye (choroid and retina), while not easily be absorbed by the lens.
本研究旨在确定兔眼眼周注射甲泼尼龙琥珀酸钠（MPSS）后，其及其代谢产物甲泼尼龙（MP）在血浆和眼组织中的药代动力学及分布情况。48只健康的新西兰白兔被随机分为12组，包括对照组和11个在不同时间点取样的MPSS治疗组。MPSS治疗组的兔子左眼接受眼周注射MPSS（10mg）。采用液相色谱串联质谱法（LC-MS/MS）研究MPSS和MP在血浆和眼组织（包括房水、玻璃体、虹膜、晶状体、巩膜、视神经、脉络膜和视网膜）中的药代动力学。眼周注射后，MPSS在眼组织中的达峰时间（ ）为0.25小时至1小时，在血浆中为0.25小时。MP在眼组织中的达峰时间为0.5小时至6小时，在血浆中为0.5小时。MPSS和MP在眼组织中的最大浓度（ ）及曲线下面积（AUC ）从高到低依次为巩膜、视神经、脉络膜和视网膜、虹膜和晶状体。特别是，与其他眼组织相比，晶状体中MPSS和MP的浓度要低得多。眼周给药后，MPSS可在眼组织中迅速代谢为其活性成分MP。此外，MPSS可有效递送至眼后段（脉络膜和视网膜），而不易被晶状体吸收。
