Pharmacokinetics after Periocular Methylprednisolone Sodium Succinate Injection in Rabbit Eyes

Abstract

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 (T _max) of MPSS ranged from 0.25 h to 1 h in ocular tissues and was 0.25 h in plasma. T _max of MP in ocular tissues ranged from 0.5 h to 6 h, and T _max of MP in plasma was 0.5 h. The maximum concentration (C _max) of MPSS and MP and the area under the curve (AUC_0-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.

Figure 1

Full scan product ion spectra of [M-H]⁻ for MPSS (a), MP (b), and dexamethasone (c).

Figure 2

Representative multiple reaction monitoring chromatograms of MPSS, MP, and dexamethasone in rabbit blood plasma: (a) blank plasma sample; (b) plasma sample spiked with MPSS (0.3 ng/ml), MP (3 ng/ml), and dexamethasone (1000 ng/ml); (c) plasma sample obtained when concentration was highest after administration of MPSS in healthy rabbits (I for MPSS, II for MP, and Ш for dexamethasone).