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B. A. Jessen, S. Khoh-Reiter, S. Riley, G. Prasanna; Corneal Safety of the Topical Ocular Formulation Preservative Benzalkonium Chloride in Xalatan and Its Vehicle. Invest. Ophthalmol. Vis. Sci. 2007;48(13):379.
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Benzalkonium chloride (BAK) is a common preservative found in topical ocular formulations. The purpose of the current studies was to evaluate and compare the safety of clinical formulations of pharmacologically active ophthalmic drugs that contain BAK with those lacking the preservative, in an in vitro model and determine the relevance to in vivo monkey corneal observations.
XalatanÂ® and PatanolÂ®, containing BAK, and Travatan-ZÂ®, without BAK, were applied to Skinethic corneal epithelial cultures for 10 or 25 minutes at 37ÂºC followed by evaluation of cellular viability. In a monkey study, one group of cynomolgus monkeys (N=3/gender) was dosed BID with the latanoprost vehicle containing 0.02% BAK in one eye, while the other eye was untreated. In the other group of monkeys (N=5/gender), one eye was dosed with the vehicle while the other eye received 6 Âµg/day (3 Âµg BID) of latanoprost solution (the active ingredient in Xalatan) containing 0.02% BAK. Pachymetry was performed prior to dosing and on 4, 13, 26, and 52 weeks after study initiation.
There was no corneal toxicity with any of the drug products at the 10 min time point in the in vitro corneal Skinethic model. Compared to the saline control, at the 25 min time point there was a minimal decrease in viability with all the drugs that was independent of the presence of BAK. Additionally, in the 1-year monkey study, there was no difference in corneal thickness at any time point between the untreated and vehicle- treated eyes of the first group of monkeys, or between the vehicle-treated eyes and the latanoprost-treated eyes of the other group.
These results demonstrate the corneal safety of latanoprost and its vehicle containing 0.02% BAK dosed at twice the frequency of the clinically recommended dosing regimen dosed up to 1-year in monkeys. Further, observations in the Skinethic human corneal epithelial system also confirm the corneal safety of Xalatan and its vehicle (containing 0.02% BAK) and demonstrate no difference between the corneal safety of Xalatan and Travatan-Z. Results from the in vitro model appear to be consistent with the long-term in vivo observations, thus demonstrating the usefulness and validity of both models in assessing corneal safety.
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