RESUMEN
The effects on intraocular pressure of the novel topical carbonic anhydrase inhibitor MK-927 were investigated for the first time in patients. Three drops of 2% MK-927 was administered in a two-center, double-masked, randomized, placebo-controlled, two-period crossover study in 25 patients with bilateral primary open angle glaucoma or ocular hypertension. At 4.5 hours after the dose, MK-927-treated eyes demonstrated a peak mean change of -7.7 mm Hg from a mean intraocular pressure of 27.8 mm Hg immediately before the dose; this compares with a change of -3.9 mm Hg from a mean intraocular pressure of 28.2 mm Hg when the same eyes were treated with placebo. The peak mean percent change in intraocular pressure in eyes treated with MK-927 was -26.7% at 6 hours after the dose compared with a change of -13.7% after treatment with placebo. No contralateral effect on intraocular pressure due to MK-927 was observed.
Asunto(s)
Inhibidores de Anhidrasa Carbónica/uso terapéutico , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Hipertensión Ocular/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Tiofenos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de Anhidrasa Carbónica/administración & dosificación , Ensayos Clínicos como Asunto , Método Doble Ciego , Color del Ojo , Femenino , Humanos , Presión Intraocular/efectos de los fármacos , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas , Placebos , Distribución Aleatoria , Sulfonamidas/administración & dosificación , Tiofenos/administración & dosificaciónRESUMEN
A three-dose, randomized, double-masked, parallel, placebo-controlled ocular tolerance study was undertaken in 12 healthy, normal volunteers with the water-soluble, topical carbonic anhydrase inhibitor MK-927. To our knowledge, this constitutes the first administration of MK-927 to humans. Ten subjects received three drops of 2% MK-927 ophthalmic solution and two subjects received three drops of placebo (vehicle) in one randomly selected eye. Local tolerance of 2% MK-927 was acceptable and supports further clinical trials in patients. Significant intraocular pressure (IOP)-lowering activity was noted when comparing IOP four hours after first dose with that 20 hours predose in the treated eye of subjects receiving MK-927 (mean percent change in IOP, -29.7%; mean change in IOP, -4.6 mm Hg) as opposed to the same comparison for the contralateral, untreated eye (-7.2% and -1.3 mm Hg, respectively). In the two subjects treated with placebo, IOP-lowering activity was not seen in either the placebo-treated eye (-0.4%) or the contralateral, untreated eye (+3.1%).