June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device
Author Affiliations & Notes
  • Nobuhiro Nagai
    Graduate School of Medicine, Tohoku University, Sendai, Japan
  • Yasuko Izumida
    Graduate School of Medicine, Tohoku University, Sendai, Japan
  • Eri Koyanagi
    Graduate School of Medicine, Tohoku University, Sendai, Japan
  • Hirokazu Kaji
    Graduate School of Engineering, Tohoku University, Sendai, Japan
  • Matsuhiko Nishizawa
    Graduate School of Engineering, Tohoku University, Sendai, Japan
  • Takahito Imagawa
    R-tech Ueno Ltd., Tokyo, Japan
  • Akiko Morikawa
    R-tech Ueno Ltd., Tokyo, Japan
  • Toru Nakazawa
    Graduate School of Medicine, Tohoku University, Sendai, Japan
  • Yukihiko Mashima
    R-tech Ueno Ltd., Tokyo, Japan
  • Toshiaki Abe
    Graduate School of Medicine, Tohoku University, Sendai, Japan
  • Footnotes
    Commercial Relationships Nobuhiro Nagai, Tohoku University (P); Yasuko Izumida, None; Eri Koyanagi, None; Hirokazu Kaji, Tohoku University (P); Matsuhiko Nishizawa, Tohoku University (P); Takahito Imagawa, R-tech Ueno Ltd. (E); Akiko Morikawa, R-tech Ueno Ltd. (E); Toru Nakazawa, None; Yukihiko Mashima, R-tech Ueno Ltd. (E); Toshiaki Abe, Tohoku University (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4153. doi:
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      Nobuhiro Nagai, Yasuko Izumida, Eri Koyanagi, Hirokazu Kaji, Matsuhiko Nishizawa, Takahito Imagawa, Akiko Morikawa, Toru Nakazawa, Yukihiko Mashima, Toshiaki Abe; Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4153.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To evaluate the ocular tissue distribution of unoprostone isopropyl (UNO) and retinal toxicity after transscleral administration of UNO by a drug delivery device in rabbits.

Methods: The device consists of a reservoir, controlled-release cover, and drug formulation, which were made of photopolymeized poly(ethyleneglycol) dimethacrylates. UNO, a prostone and BK channel activator for antiglaucoma eyedrops marketed in Japan, was loaded in the device (length, 10 mm; width, 3.6 mm; height, 0.7 mm) at a content of 2.85 mg UNO. High-performance liquid chromatography was used to evaluate the release amount of UNO in vitro. The UNO metabolite, unoprostone-free acid (M1), concentrations in the retina, choroid, and plasma were determined by liquid chromatography-tandem mass spectrometry at 4, 12, and 24 weeks after implantation in rabbits. Retinal toxicity was evaluated by electroretinogram and optical coherence tomography.

Results: The UNO released from the device in vitro showed zero-ordered kinetics for 12 weeks, then the release gradually decreased to 24 weeks. The area under the M1 concentration curve (AUC) of the retina during 24-week device implantation was higher than the simulated AUC of the retina after topical administration of 0.12% UNO eye-drop (once-a-day for 24-week). No substantial toxic reactions were observed by electroretinogram and optical coherence tomography.

Conclusions: The device could be a useful carrier for intraocular sustained delivery of UNO without producing severe retinal toxicity.

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