RESUMEN
AIMS: To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD). METHODS: Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received pegaptanib. At 102 weeks, subjects receiving pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3. RESULTS: As in years 1 and 2, pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to pegaptanib treatment. CONCLUSION: The 3-year safety profile of pegaptanib sodium was favourable in patients with NV-AMD.
Asunto(s)
Aptámeros de Nucleótidos/efectos adversos , Neovascularización Coroidal/prevención & control , Degeneración Macular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Femenino , Angiografía con Fluoresceína , Humanos , Presión Intraocular/efectos de los fármacos , Masculino , Tonometría Ocular , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the safety of pegaptanib sodium injection, a specific vascular endothelial growth factor (VEGF) antagonist, in the treatment of neovascular age-related macular degeneration (AMD) during 2 years of therapy. DESIGN: Two concurrent, prospective, randomized, multicenter, double-masked, sham-controlled studies. METHODS: Patients with all angiographic choroidal neovascularization lesion compositions of AMD received either intravitreous pegaptanib sodium (0.3 mg, 1 mg, 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks; sham-treated patients were re-randomized (1:1:1:1:1) to continue sham, discontinue, or receive one of the pegaptanib doses. MAIN OUTCOME MEASURES: All reported adverse events, serious adverse events, and deaths. PARTICIPANTS: In year 1, 1190 subjects received at least one study treatment (0.3 mg, n = 295; 1 mg, n = 301; 3 mg, n = 296; sham, n = 298); 7545 intravitreous injections of pegaptanib were administered. In year 2, 425 subjects (0.3 mg, n = 128; 1 mg, n = 126; 3 mg, n = 120; sham, n = 51) continued the same masked treatment as in year 1 and received at least one study treatment in year 2; 2663 intravitreous injections of pegaptanib were administered in these subjects. RESULTS: All doses of pegaptanib were well tolerated. The most common ocular adverse events were transient, mild to moderate in intensity, and attributed to the injection preparation and procedure. There was no evidence of an increase in deaths, in events associated with systemic VEGF inhibition (e.g., hypertension, thromboembolic events, serious hemorrhagic events), or in severe ocular inflammation, cataract progression, or glaucoma in pegaptanib-treated patients relative to sham-treated patients. In year 1, serious injection-related complications included endophthalmitis (12 events, 0.16%/injection), retinal detachment (RD) (6 events [4 rhegmatogenous, 2 exudative], 0.08%/injection), and traumatic cataract (5 events, 0.07%/injection). Most cases of endophthalmitis followed violations of the injection preparation protocol. In patients receiving pegaptanib for >1 year, there were no reports of endophthalmitis or traumatic cataract in year 2; RD was reported in 4 patients (all rhegmatogenous, 0.15%/injection). CONCLUSION: The 2-year safety profile of pegaptanib sodium is favorable in patients with exudative AMD.
Asunto(s)
Aptámeros de Nucleótidos/uso terapéutico , Neovascularización Coroidal/tratamiento farmacológico , Degeneración Macular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Aptámeros de Nucleótidos/efectos adversos , Neovascularización Coroidal/etiología , Método Doble Ciego , Femenino , Angiografía con Fluoresceína , Humanos , Inyecciones , Presión Intraocular/efectos de los fármacos , Degeneración Macular/complicaciones , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/efectos de los fármacos , Cuerpo VítreoRESUMEN
CS-866, a novel angiotensin II receptor blocker, is rapidly and completely metabolized to RNH-6270, its active metabolite. The pharmacokinetics of RNH-6270 following oral CS-866 or intravenous RNH-6270 administration was determined in 104 healthy male volunteers. The pharmacokinetics of RNH-6270 was linear over dose ranges of 1 to 32 mg (intravenous RNH-6270 administration) and 10 to 160 mg (oral CS-866 administration). The time to maximum plasma concentration of RNH-6270 after oral CS-866 administration ranged from 1.4 to 2.8 hours, and the terminal elimination half-life ranged from 12 to 18 hours. Absolute bioavailability of RNH-6270 after oral administration of CS-866 was 26%. Administration of CS-866 once daily for 10 days did not result in drug accumulation. When administered intravenously, RNH-6270 has a volume of distribution of 15 to 25 L. Approximately 35% to 50% of RNH-6270 is excreted unchanged in the urine. CS-866 was safe and well tolerated at doses of up to 160 mg/day.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Imidazoles/sangre , Imidazoles/orina , Tetrazoles/sangre , Tetrazoles/orina , Administración Oral , Adulto , Área Bajo la Curva , Disponibilidad Biológica , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Hipotensión/inducido químicamente , Imidazoles/administración & dosificación , Imidazoles/efectos adversos , Infusiones Intravenosas , Hígado/enzimología , Masculino , Tasa de Depuración Metabólica , Enfermedades Musculoesqueléticas/inducido químicamente , Olmesartán Medoxomilo , Dolor/inducido químicamente , Comprimidos , Tetrazoles/administración & dosificación , Tetrazoles/efectos adversos , Transaminasas/efectos de los fármacosRESUMEN
Several parameters of aqueous humor dynamics were measured in 11 human subjects before and after exposure of one eye to a continuous stream of cold air. In the treated eye, I.O.P. was found to decrease significantly from a mean +/- SD pre-treatment value of 14.1 +/- 2.3 mmHg to a post-treatment value of 12.6 +/- 2.6 mmHg. Episcleral venous pressure was found to decrease significantly from a pre-treatment value of 6.2 +/- 1.3 mm Hg. No significant changes were found in aqueous flow or total outflow facility, indicating that cold air exposure decreased I.O.P. by causing a decrease in episcleral venous pressure.
Asunto(s)
Aire , Humor Acuoso/fisiología , Frío , Temperatura Corporal , Humanos , Presión Intraocular , Esclerótica/irrigación sanguínea , Factores de Tiempo , Presión VenosaRESUMEN
We treated 20 recently postoperative eyes with nonfunctioning trabeculectomies at the site of the failed bleb with two to four ultrasound applications, each of five seconds duration, at an intensity level of 10 kW/cm2. Fifteen of the eyes demonstrated a long-term decrease in intraocular pressure to 21 mm Hg or below. The mean intraocular pressure of all patients fell from a preultrasound mean (+/- S.D.) of 32 +/- 8 mm Hg to 20 +/- 10 mm Hg at a mean time of 236 +/- 204 days postultrasound. Complications included an immediate postultrasound rise in pressure over 10 mm Hg in 13 eyes, and the immediate development of a cataract in one patient.