Literature DB >> 18696099

Tolerability of N-chlorotaurine plus ammonium chloride in the rabbit and human eye--a phase 1 clinical study.

Barbara Teuchner1, Eduard Schmid, Hanno Ulmer, Waldemar Gottardi, Markus Nagl.   

Abstract

BACKGROUND: N-chlorotaurine (NCT), an endogenous mild antiseptic, is well-tolerated by application to the human conjunctiva and has been shown to offer beneficial effects in infectious conjunctivitis. Animal tests revealed improved efficacy of a combination of NCT with ammonium chloride in adenoviral conjunctivitis. The aim of this study was to evaluate the tolerability of NCT plus ammonium chloride in the healthy rabbit and human eye.
METHODS: First, a tolerability study was performed in rabbits. In a blinded and randomized fashion, one eye was treated with the test medication, the other one with 0.9% saline. Twenty-one animals (three per concentration) were treated with one drop every 2 hours for 6 days. Second, in two volunteers one drop of a defined concentration was applied to one eye every 15 min for 1 hour, saline to the control eye. Four different concentrations were tested on different days. Third, a double-blind, randomized phase 1 study in 13 healthy volunteers was performed. One drop of 0.1% NCT plus 0.1% NH(4)Cl versus saline was applied every 15 min within the first hour, followed by four drops every 2 hours. This regimen was done daily for 5 days.
RESULTS: In rabbits, no side effects were seen with 0.1% NCT plus 0.1% NH(4)Cl, while higher concentrations sometimes caused short-time and minimal conjunctival injection and secretion after dosing. By 1% NCT plus 1% NH(4)Cl, these effects were moderate, but disappeared again without any detectable residues. In the pilot study with two volunteers, treatment with 0.5% NCT plus 0.1% NH(4)Cl caused medium-scale eye burning for 30 seconds, while 0.1% NCT plus 0.1% NH(4)Cl was very well-tolerated, with no or minimal burning for a few seconds. In the subsequent phase 1 study, 0.1% NCT plus 0.1% NH(4)Cl was well-tolerated by all subjects except for minimal eye burning for a few seconds after dropping. No objective signs of eye changes could be detected in the human beings.
CONCLUSION: The results of this study clearly demonstrate the good tolerability of a promising NCT formulation with improved activity.

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Year:  2008        PMID: 18696099     DOI: 10.1007/s00417-008-0900-x

Source DB:  PubMed          Journal:  Graefes Arch Clin Exp Ophthalmol        ISSN: 0721-832X            Impact factor:   3.117


  21 in total

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Authors:  M Nagl; M W Hess; K Pfaller; P Hengster; W Gottardi
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7.  Tolerance of N-chlorotaurine, a new antimicrobial agent, in infectious conjunctivitis - a phase II pilot study.

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3.  Reexamining Ophthalmic Drugs, Safety and Tolerability in Phase 1 Clinical Trials.

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4.  Tolerability of inhaled N-chlorotaurine in the pig model.

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  4 in total

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