Distribution of topical ocular nepafenac and its active metabolite amfenac to the posterior segment of the eye

作者：James E. Chastain, Mark Sanders, Michael A. Curtis, Nagendra Chemuturi, Martha E. Gadd, Michael A. Kapin, KERRY L. MARKWARDT, David C. Dahlin · 发表于：Experimental Eye Research · 年份：2015 · DOI：10.1016/j.exer.2015.10.009 · 被引用次数：53 · 研究领域：Inflammatory mediators and NSAID effects、Retinal Diseases and Treatments、Glaucoma and retinal disorders

Nepafenac ophthalmic suspensions, 0.1% (NEVANAC(®)) and 0.3% (ILEVRO™), are topical nonsteroidal anti-inflammatory drug (NSAID) products approved in the United States, Europe and various other countries to treat pain and inflammation associated with cataract surgery. NEVANAC is also approved in Europe for the reduction in the risk of postoperative macular edema (ME) associated with cataract surgery in diabetic patients. The efficacy against ME suggests that topical administration leads to distribution of nepafenac or its active metabolite amfenac to the posterior segment of the eye. This article evaluates the ocular distribution of nepafenac and amfenac and the extent of local delivery to the posterior segment of the eye, following topical ocular instillation in animal models. Nepafenac ophthalmic suspension was instilled unilaterally in New Zealand White rabbits as either a single dose (0.1%; one drop) or as multiple doses (0.3%, one drop, once-daily for 4 days, or 0.1% one drop, three-times daily for 3 days and one morning dose on day 4). Nepafenac (0.3%) was also instilled unilaterally in cynomolgus monkeys as multiple doses (one drop, three-times daily for 7 days). Nepafenac and amfenac concentrations in harvested ocular tissues were measured using high-performance liquid chromatography/mass spectrometry. Locally-distributed compound concentrations were determined as the difference in levels between dosed and undosed eyes. In single-dosed rabbit eyes, peak concentrations ...