Pharmacokinetics after Periocular Methylprednisolone Sodium Succinate Injection in Rabbit Eyes

摘要

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 (Tmax) of MPSS ranged from 0.25?h to 1?h in ocular tissues and was 0.25?h in plasma. Tmax of MP in ocular tissues ranged from 0.5?h to 6?h, and Tmax of MP in plasma was 0.5?h. The maximum concentration (Cmax) of MPSS and MP and the area under the curve (AUC0-t) 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.