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Title: Ocular Distribution and Pharmacokinetics of 8-Oxo-2'-Deoxyguanosine: A Novel Therapeutic Candidate of Ocular Surface Diseases. Author: Chung H, Ha Y, Kim YH, Kim DH, Shin D. Journal: J Ocul Pharmacol Ther; 2022 Oct; 38(8):561-566. PubMed ID: 36288559. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]