In vitro studies of antiglaucomatous prostaglandin analogues: travoprost with and without benzalkonium chloride and preserved latanoprost.

Abstract

PURPOSE:

With use of the Wong-Kilbourne derivative Chang conjunctival cell line, this study compared in vitro the ocular toxicity of three topical intraocular pressure (IOP)-lowering agents: travoprost 0.004% containing 0.015% benzalkonium chloride (BAK), travoprost Z 0.004%, a new formulation without BAK, and latanoprost 0.005% containing 0.02% BAK.

METHODS:

Neutral red, Alamar blue, YOPRO-1, and annexin V/7-AAD assays were used to evaluate the effects of the IOP-lowering agents and BAK on cellular viability, membrane integrity, and apoptosis in the conjunctival cell line using microtitration fluorometric analysis and flow cytometry. All assessments were performed in a masked manner.

RESULTS:

Assessment of cell viability and membrane integrity revealed a significant effect by latanoprost with BAK or BAK alone but no effect by travoprost Z without BAK or buffer alone (P < 0.0001). Latanoprost with BAK, travoprost with BAK, and BAK alone were cytotoxic in Chang conjunctival cells, whereas no cytotoxicity was observed in cells exposed to travoprost Z without BAK or in cells treated with buffer (P < 0.0001). No increase in apoptosis or necrosis was observed in cells treated with control or travoprost Z without BAK compared with BAK, travoprost with BAK, and latanoprost with BAK (P < 0.0001).

CONCLUSIONS:

Latanoprost with BAK, travoprost with BAK, and BAK alone have significant cytotoxic effects on human conjunctiva-derived cells and are associated with apoptosis. These effects likely result from BAK used as a preservative. IOP-lowering agents with alternative preservatives instead of BAK will most likely have fewer ocular surface adverse effects than agents containing BAK.

• Authors: Christophe Baudouin, Luisa Riancho, Jean-Michel Warnet, Françoise Brignole
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 48 Issue 9 Pg. 4123-8 (Sep 2007) ISSN: 0146-0404 [Print] United States
• PMID: 17724196 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Antihypertensive Agents
• Benzalkonium Compounds
• Preservatives, Pharmaceutical
• Prostaglandins F, Synthetic
• Cloprostenol
• Latanoprost
• Travoprost

Topics

• Annexin A5
• Antihypertensive Agents (toxicity)
• Apoptosis (drug effects)
• Benzalkonium Compounds (toxicity)
• Cell Line
• Cell Membrane (drug effects)
• Cell Survival (drug effects)
• Cloprostenol (analogs & derivatives, toxicity)
• Conjunctiva (drug effects, pathology)
• Drug Therapy, Combination
• Flow Cytometry
• Glaucoma (drug therapy)
• Humans
• Intraocular Pressure (drug effects)
• Latanoprost
• Necrosis
• Preservatives, Pharmaceutical (toxicity)
• Prostaglandins F, Synthetic (toxicity)
• Travoprost