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Oktay Uzun, Ankita Desai, Sanjani Ray, Chintan Patel, Charles D Blizzard, Peter K Jarrett, Michael Goldstein; Pharmacokinetics of a Hydrogel-based Nepafenac Intracanalicular Insert in Canines. Invest. Ophthalmol. Vis. Sci. 2022;63(7):447.
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© ARVO (1962-2015); The Authors (2016-present)
Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are often prescribed following ophthalmic surgery to reduce ocular pain and modulate inflammation. Sustained-release drug delivery of NSAIDs may overcome some limitations of topical therapy such as patient self-dosing and nonadherence. Here we evaluate the pharmacokinetics of nepafenac delivered from a biodegradable hydrogel intracanalicular insert in a canine model.
A hydrogel-based intracanalicular insert containing a low dose of nepafenac was placed bilaterally into the inferior canaliculus of 20 beagle dogs on Day 0. After presence of the insert in the canaliculus was confirmed visually, tear fluid was collected from n=10 eyes with pre-cut 10 mm Schirmer test strips at 2 hours, and 1, 3, 7, 10, 14, 17, 21, 24 and 28 days post-insertion. Aqueous humor (0.1 mL, n=6 eyes) was collected 7, 14, 21, and 28 days post-insertion. Tear fluid and aqueous humor samples were analyzed for nepafenac (prodrug) and amfenac (active metabolite) by liquid chromatography tandem mass spectrometry.
Maximum mean concentration of nepafenac (671 ng/mL) and amfenac (153 ng/mL) in the tear fluid was measured at 2 hours post-insertion indicating rapid dissolution of drug from the insert soon after placement. Mean nepafenac and amfenac levels in tear fluid samples over time showed drug levels gradually tapered over time. Nepafenac and amfenac levels were cleared from the tear fluid by 10-14 days. Both the prodrug and active metabolite were found in the tear fluid in an 85:15 ratio, however, only amfenac was detected in aqueous humor samples. Amfenac concentration in the aqueous humor was highest on Day 7 at 18.3 ng/mL and decreased to 2.6 ng/mL at Day 14. Levels of amfenac in the aqueous humor were 41-fold above the half maximal inhibitory concentration of cyclooxygenase-2 for amfenac (COX-2 IC50 = 0.45 ng/mL) indicating potential therapeutic benefit at these concentrations.
A hydrogel-based intracanalicular insert containing nepafenac quickly released drug at therapeutic levels to the ocular surface and continued for 10-14 days. Ocular pharmacokinetic studies of inserts with higher drug doses are needed to further characterize the release profile of nepafenac intracanalicular insert.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
Nepafenac Intracanalicular Insert Tear Fluid Pharmacokinetics
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