Ocular Distribution and Pharmacokinetics of 8-Oxo-2′-Deoxyguanosine: A Novel Therapeutic Candidate of Ocular Surface Diseases

药代动力学 最大值 结膜 角膜 睫状体 化学 分布(数学) 药理学 分配量 生物利用度 医学 眼科 病理 数学 数学分析
作者
Hyewon Chung,Yuseung Ha,Yong Ho Kim,Dong Hyun Kim,Dong Wan Shin
出处
期刊:Journal of Ocular Pharmacology and Therapeutics [Mary Ann Liebert, Inc.]
卷期号:38 (8): 561-566
标识
DOI:10.1089/jop.2022.0054
摘要

Purpose: This study evaluated the ocular distribution and plasma pharmacokinetics (PKs) of 8-oxo-2′-deoxyguanosine (8-oxo-dG) in rabbits and rats, respectively. Methods: A test formulation containing radiolabeled [14 C]8-oxo-dG and unlabeled 8-oxo-dG was ocularly administered to rabbits as a single dose of 1 mg per body and intravenously injected to rats as a single dose of 5 mg/kg. The ocular distribution of [14 C]8-oxo-dG was evaluated using autoradiography until 48 h postdose. Plasma radioactivity in rabbits and rats was determined until 72 and 168 h, respectively. Results: After ocular instillation, [14 C]8-oxo-dG distributed into ocular tissues, and high radioactivity concentrations were observed in the ciliary body, conjunctiva, and cornea. The maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC0-t) were highest in the ciliary body and conjunctiva, respectively. In the conjunctiva, cornea, and aqueous humor, time to reach Cmax (Tmax) was 0.5 h, and the half-lives were 11.2, 30.2, and 15.1 h, respectively. The radioactivity of [14 C]8-oxo-dG in plasma of rabbits displayed a double-peak phenomenon with the second peak considered as Cmax (37.9 ± 3.1 ng eq./mL) occurring 24 h postdose. After systemic exposure of [14 C]8-oxo-dG in rats, a rapid decline in the initial phase and a terminal half-life of 56.1 ± 31.3 h were observed. Conclusions: Rapid ocular distribution and high concentrations in anterior ocular tissues with minimal systemic exposure were observed after the ocular instillation of 8-oxo-dG in rabbits. These PK profiles are favorable for the treatment of ocular surface diseases.
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