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Robin J Goody, Vernard Woodley, Steve Henry, Matthew S Lawrence, Céline Olmiere; Intraocular pressure lowering effects of T2347 in normotensive nonhuman primates following once-daily topical administration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1253.
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© ARVO (1962-2015); The Authors (2016-present)
Formulations combining multiple existing standards of care can provide improved intraocular pressure (IOP) lowering effects versus single drug strategies but with the pitfall of preservative overuse. The IOP lowering effects of a novel formulation of 0.5% timolol / 0.005% latanoprost (T2347) designed without preservative were compared with those of Xalacom® (0.5% timolol and 0.005% latanoprost) in normotensive St. Kitts green monkeys (Chlorocebus sabaeus).
All animals were treated in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. All procedures were conducted in normotensive monkeys following their sedation with ketamine (8 mg/kg) and xylazine (1.6 mg/kg). Strict timing of body position and IOP measurement with respect to sedation mitigated sedation effects on IOP. Twelve monkeys (n=24 eyes) previously demonstrating an IOP lowering response to Xalacom (timolol/latanoprost responders) were employed in a cross-over study design comparing IOP changes in response to 4 once-daily A.M. doses of Xalacom or T2347. Rebound tonometry (Tono Vet, iCare, Finland) was performed prior to each dose on days 1 to 4 and at 12, 16, 20 and 24 hours after the final dose.
Xalacom and T2347 elicited progressive modest decreases in IOP as assessed during once-daily evaluations immediately prior to re-dosing (i.e. approximately 24 hours after the previous dose). Significant IOP lowering from pre-treatment levels was observed for both T2347 (P<0.0001) and Xalacom (P=0.002) 12 hours after the final dose. IOP lowering effect of T2347 was sustained up to 20 hours after the last dose while significant Xalacom-induced IOP lowering effects were limited to the 12 hour time point only. Despite more sustained IOP lowering effects, T2347 did not lower IOP significantly beyond that achieved by Xalacom. The average maximal IOP lowering effect was 6.0 mmHg for T2347 and 5.6 mmHg for Xalacom with mean decrease from baseline of -4.3mmHg for T2347 and -3.6 mmHg for Xalacom and these differences were not statistically significant.
Topical administration of the novel preservative-free latanoprost/timolol formulation T2347 resulted in significant IOP lowering in normotensive monkeys similar to that induced by Xalacom though persisting up to 8 hours longer after dosing. T2347 may offer improved control of IOP versus once-daily Xalacom.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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