Absence of preservative linked with less toxicity in study

Lynda Charters

Fort Lauderdale, FL-A study that compared the toxicity of two antiglaucoma drugs, travoprost 0.004% (Travatan, Alcon Laboratories) without the preservative benzalkonium chloride with that of latanoprost 0.005% (Xalatan, Pfizer) with 0.02% benzalkonium chloride, found that the absence of the preserving agent was associated with significantly less toxicity in immortalized human corneal epithelial cells, reported Richard W. Yee, MD, at the annual meeting of the Association for Research in Vision and Ophthalmology.

Fort Lauderdale, FL-A study that compared the toxicity of two antiglaucoma drugs, travoprost 0.004% (Travatan, Alcon Laboratories) without the preservative benzalkonium chloride with that of latanoprost 0.005% (Xalatan, Pfizer) with 0.02% benzalkonium chloride, found that the absence of the preserving agent was associated with significantly less toxicity in immortalized human corneal epithelial cells, reported Richard W. Yee, MD, at the annual meeting of the Association for Research in Vision and Ophthalmology.

The difference in the toxicity between the two agents may affect patient tolerability, according to Dr. Yee. The authors published their findings in Advances in Therapy (2006;23:511-518).

While benzalkonium chloride is a widely used, effective preservative, its use over the long term in a chronic condition such as glaucoma, may have lasting adverse effects on the eyes, such as tear film instability, disruption of the corneal epithelial barrier, and even cell death if the dose is sufficiently high. In antiglaucoma medications, the concentrations of benzalkonium chloride range from 0.004% to 0.02%. A factor that compounds this potential for damage is that many patients use more than one antiglaucoma medication.

Six groups examined

In this study, the human epithelial cells were divided into six groups and subjected to different environments. Two groups were negative controls that were exposed to gentamicin and 70% methanol. Two groups were live controls; one group was in corneal epithelial culture medium and the other in hydroxypropyl-guar lubricant eye drop. In the last two groups, the human epithelial cells were exposed for 25 minutes to 100 μl of two antiglaucoma drugs. The investigators used a live/dead assay to measure the effect of the two drugs on the cells.

Dr. Yee reported that the live controls and the cells in the eye drop solution showed little or no toxic effects. The negative control portion of the experiment showed gentamicin and 70% methanol to be highly toxic to the cells. The cells that were exposed to travoprost without the preservative had a high number of living cells, and the cells exposed to latanoprost with the preservative had a high proportion of dead cells. Interestingly, Dr. Yee noted the degree of toxicity seen in the negative control group and that caused by latanoprost were not significantly different.

When the investigators measured the percentages of cells that survived, they found the following: 56.2% for travoprost compared with 5.1% for latanoprost, 7.6% for gentamicin, and 5.5% for methanol.

"We found that all three agents, travoprost, latanoprost, and gentamicin, had toxic effects on the human epithelial cells," Dr. Yee concluded. "However, that caused by travoprost was significantly less than that caused by latanoprost. The difference in the degree of toxicity may ultimately affect how patients can tolerate these drugs when treating a chronic disease such as glaucoma. The development of a prostaglandin analogue with another preservative may be more beneficial for patients who must be subjected to long-term treatment regimens."