RT Journal Article
A1 Nagai, Nobuhiro
A1 Yamada, Shinji
A1 Kawasaki, Junichi
A1 Koyanagi, Eri
A1 Saijo, Saaya
A1 Kaji, Hirokazu
A1 Nishizawa, Matsuhiko
A1 Nakazawa, Toru
A1 Abe, Toshiaki
T1 Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes
JF Investigative Ophthalmology & Visual Science
JO IOVS
YR 2018
DO 10.1167/iovs.17-22429
JF Investigative Ophthalmology & Visual Science
VO 59
IS 2
SP 644
OP 652
SN 1552-5783
AB    We evaluate the ocular tissue distribution and retinal toxicity of unoprostone (UNO) during 12 months, after transscleral sustained-UNO administration using a drug delivery device in monkey eyes.    The device consisted of a reservoir, controlled-release cover, and a drug formulation of photopolymerized polyethylene glycol dimethacrylate. Six mg UNO was loaded into the device (length, 17 mm; width, 4.4 mm; height, 1 mm). The concentrations of M1, a primary metabolite of UNO, in the retina, choroid, vitreous, lens, aqueous humor, iris, ciliary body, and plasma were determined by liquid chromatography-tandem mass spectrometry at 3, 6, and 12 months after implantation. Retinal toxicity was evaluated by electroretinography (ERG), optical coherence tomography (OCT), and IOP at preimplantation, and at 6, 9, and 12 months after implantation. Focal ERGs were performed at 9 and 12 months after implantation.    M1 was detected in the choroid and retina with maximum peaks of 243.2 and 8.41 ng/g at 6 months, respectively. M1 in the ciliary body and iris was detected with maximum peaks of 7.66 and 10.4 ng/g at 6 and 12 months, respectively. Less than 1 ng/mL or ng/g of M1 was detected in the aqueous humor, vitreous, and lens. No changes were observed in retinal function as assessed by ERG, IOP, or macula thickness and retinal histology by OCT examinations during the 12-month period. No differences in focal ERG amplitudes, especially in the macula, were observed.    The device provided intraocular sustained delivery of UNO for 12 months without producing severe retinal toxicity.  
RD 12/9/2019
UL https://doi.org/10.1167/iovs.17-22429