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Clinical Pharmacokinetics

, Volume 44, Issue 3, pp 247–261 | Cite as

Ocular Pharmacokinetics and Safety of Ciclosporin, a Novel Topical Treatment for Dry Eye

Review Article

Abstract

Ciclosporin is a potent immunomodulator that acts selectively and locally when administered at the ocular surface. 0.05% ciclosporin ophthalmic emulsion has recently been approved by the US FDA for treatment of keratoconjunctivitis sicca (KCS) [dry-eye disease].

After topical application, ciclosporin accumulates at the ocular surface and cornea, achieving concentrations (≥0.236 μg/g) that are sufficient for immunomodulation. Very little drug penetrates through the ocular surface to intraocular tissues. Ciclosporin is not metabolised in rabbit or dog eyes and may not be prone to metabolism in human eyes. Cultured human corneal endothelial and stromal cells exposed to ciclosporin in vitro exhibited no adverse effects and only minor effects on DNA synthesis. No ocular or systemic toxicity was seen with long-term ocular administration of ciclosporin at concentrations up to 0.4%, given as many as six times daily for 6 months in rabbits and 1 year in dogs. Systemic blood ciclosporin concentration after ocular administration was extremely low or undetectable in rabbits, dogs and humans, obviating concerns about systemic toxicity. In 12-week and 1-year clinical safety studies in dry-eye patients, the most common adverse event associated with the ophthalmic use of ciclosporin emulsion was ocular burning. No serious drug-related adverse events occurred.

These data from in vitro, nonclinical and clinical studies indicate effective topical delivery of ciclosporin to desired target tissues along with a favourable safety profile, making 0.05% ciclosporin ophthalmic emulsion a promising treatment for KCS.

Keywords

Ocular Surface Lacrimal Gland Keratoconjunctivitis Sicca Ocular Administration Herpetic Stromal Keratitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors are employees of Allergan Inc., manufacturer of Restasis™. This article is a scientific review of published literature.

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© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Department of Pharmacokinetics and Drug MetabolismAllergan, Inc.IrvineUSA

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