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B.T. Gabelt, E.A. Hennes, M.A. Bendel, M. Okka, P.L. Kaufman; IOP Lowering Comparison in Monkeys: PGF2a–ie vs the Rest . Invest. Ophthalmol. Vis. Sci. 2006;47(13):217.
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Determine whether the magnitude of the intraocular pressure (IOP) lowering response to prostaglandin (PG)F2α –ie in monkeys can be attained by combining other PG subtype selective compounds.
IOP (Goldmann) dose responses were determined for 6–8 hr on days 4–5 of once (q.d.) or twice (b.i.d.) daily topical treatments with functional FP agonists latanoprost (L), bimatoprost (B), and travoprost (T); EP2 agonist butaprost (BU); EP3 agonist sulprostone (S); or PGF2α–ie (P). All agents were formulated in 20% DMSO/PBS and administered as 2 or 4, five µl drops to ketamine anesthetized normotensive cynomolgus monkeys. IOP was compared (two–tailed paired t–test) to the opposite eye and corrected for baseline prior to the initial treatment on the first day of each study.
Initial IOP before any treatments ranged from 13–23 mmHg. The optimum treatment regimen and IOP lowering responses to individual agents was as follows:
Data are mean±s.e.m. Paired eyes averaged. *The same group of monkeys was used after appropriate rest periods.
The IOP response (n=8) to the combined treatments of L (q.d.) + BU (b.i.d.) or L (q.d.) + S (b.i.d.) was not significantly greater than L alone. The combination of L (q.d.) + S (b.i.d) + BU (b.i.d) significantly decreased IOP by 3–5 mmHg more that L alone (12–18 hr post L) (p<0.01) although the response to L alone was not as great as in the other studies in the same set of monkeys.
Clinical doses of L, T and B administered q.d. pm produced maximal IOP lowering responses in normotensive monkeys compared to b.i.d treatments or 3–fold higher doses given q.d. L, T and B were similar in their efficacies. The addition of EP2 or EP3 agonists alone to L did not further enhance the IOP lowering response. However, the combined therapy with L+S+Bu decreased IOP more that L alone. Comparison of this regimen to P in the same group of animals is forthcoming.
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