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Stability, safety, and pharmacokinetics of ganciclovir eye drops prepared from ganciclovir for intravenous infusion

  • Naoki Okumura
  • Toshiyuki Tanaka
  • Yuya Fukui
  • Noriko KoizumiEmail author
Laboratory Investigation
  • 34 Downloads

Abstract

Purpose

Hospital-prepared topical ganciclovir eye drops made from intravenous infusions are used to treat cytomegalovirus corneal endotheliitis. This study assessed the efficacy of these eye drops.

Study design

Experimental study design.

Methods

Ganciclovir solutions (0.5% and 1.0%) prepared by diluting DENOSINE® IV Infusion in saline were stored light-shielded at 4, 25, or 37°C for 12 weeks. Every two weeks during storage, macroscopic evaluation was conducted and ganciclovir concentrations were determined by high performance liquid chromatography. Ocular surface toxicity and corneal ganciclovir concentrations were evaluated following topical instillation of ganciclovir solutions in rabbits.

Results

Ganciclovir solutions maintained transparency for 6 weeks, with precipitation appearing after 8 weeks. Ganciclovir concentrations were maintained at ~100% for 6 weeks at 4°C and 25°C and decreased gradually to 90% after 12 weeks. At 37°C, ganciclovir concentrations decreased linearly for 12 weeks. Rabbit eyes showed no ocular surface toxicity. Following instillation of 0.5% ganciclovir solution, endothelial ganciclovir concentrations were 28.0 µg/g at one hour and 4.3 µg/g at three hours.

Conclusions

Ganciclovir eye drops seem to be safe and penetrate the corneal endothelium. The drug in eye drop form is chemically stable for up to 6 weeks. Eye drops’ development for approval by regulatory authorities, especially with improved long-term stability, is anticipated.

Keywords

Ganciclovir eye drops Cytomegalovirus corneal endotheliitis Stability Pharmacokinetics 

Notes

Acknowledgements

The authors thank Mr. Hirofumi Imai and Mr. Tetta Kurosawa for technical support. The authors thank Scribendi.com for their professional English editing service. This study was supported by the Program for the Strategic Research Foundation at Private Universities from MEXT (Koizumi N and Okumura N).

Conflicts of interest

N. Okumura, None; T. Tanaka, None; Y. Fukui, None; N. Koizumi, None.

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Copyright information

© Japanese Ophthalmological Society 2019

Authors and Affiliations

  • Naoki Okumura
    • 1
  • Toshiyuki Tanaka
    • 1
  • Yuya Fukui
    • 1
  • Noriko Koizumi
    • 1
    Email author
  1. 1.Department of Biomedical Engineering, Faculty of Life and Medical SciencesDoshisha UniversityKyotanabeJapan

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