RESUMEN
The toxicity of rioprostil was extensively investigated. Studies in rodents, dogs and monkeys indicate a low order of acute toxicity. Oral subchronic and chronic toxicity studies in rats and dogs produce effects that would be expected based on the pharmacological activity of the compound. In reproduction studies with rioprostil, male and female fertility is unaffected in rats at doses up to 2.0 mg/kg/day and there is no evidence of embryotoxicity, fetotoxicity, or teratogenicity in rats at doses up to 1.7 mg/kg/day. In rabbits a maternally toxic dose (1.5 mg/kg) also increases resorptions, reduces fetal weight, and increases the incidence of malformations. Evaluation of 24-month carcinogenicity studies in mice and rats at oral doses up to 2.0 and 1.5 mg/kg/day, respectively, are in progress. Mutagenicity studies are negative.
Asunto(s)
Antiulcerosos/toxicidad , Prostaglandinas E/toxicidad , Animales , Pruebas de Carcinogenicidad , Femenino , Masculino , Pruebas de Mutagenicidad , Prostaglandinas Sintéticas/toxicidad , Reproducción/efectos de los fármacos , RioprostiloRESUMEN
Superficial punctate opacities were observed in the palpebral aperture region of the cornea of Sprague-Dawley and Wistar rats of both sexes and varying ages, but they were not observed in Lewis rats. Slit-lamp biomicroscopy localized the opacities in the subepithelial corneal stroma. Electron microscopy demonstrated 0.1-2.0 micron granules at the stromal-epithelial interface and in the adjacent stroma. Smaller granules, consisting of aggregates of amorphous granular material, were associated with bundles of filaments among collagen fibers. Larger granules were located adjacent to and sometimes straddle the epithelial basement membrane. The overlying epithelial cells were displaced, but otherwise appeared normal. Large granules consisted of layered dark and light electron dense rings and appeared in some instances to represent fusing of smaller granules. This rat keratopathy bears certain resemblance to granular dystrophy of man (Groenouw's Type I), but histochemically is dissimilar.
Asunto(s)
Córnea/patología , Enfermedades de la Córnea/veterinaria , Ratas Endogámicas Lew , Ratas Endogámicas , Enfermedades de los Roedores/patología , Animales , Córnea/ultraestructura , Enfermedades de la Córnea/patología , Femenino , Masculino , Microscopía Electrónica , Oftalmoscopía/veterinaria , RatasRESUMEN
Gastrointestinal irritation is the most significant side effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAID) for treatment of arthritic conditions. Rioprostil, a primary alcohol prostaglandin E1 analog, prevents gastric bleeding induced by several NSAID in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of rioprostil (50 micrograms/kg BID for 15 days) did not influence the course of the adjuvant disease in rats or alter the antiinflammatory or analgesic effect of the NSAID. In a 13 week efficacy study in dogs, rioprostil (40-60 micrograms/kg, PO) completely prevented gastric hemorrhagic lesions induced by daily administration of aspirin.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Antiulcerosos/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis/tratamiento farmacológico , Úlcera Péptica Hemorrágica/prevención & control , Prostaglandinas E/uso terapéutico , Úlcera Gástrica/complicaciones , Animales , Artritis Experimental/patología , Modelos Animales de Enfermedad , Perros , Mucosa Gástrica/patología , Masculino , Úlcera Péptica Hemorrágica/etiología , Píloro/patología , Ratas , Ratas Endogámicas Lew , Ratas Endogámicas , Rioprostilo , Úlcera Gástrica/inducido químicamenteRESUMEN
Pregnant Long-Evans Hooded rats were intravaginally administered nonoxynol-9, a non-ionic surfactant used as a spermicidal agent in Delfen Contraceptive Cream (Ortho Pharmaceutical Corporation, Raritan, N.J.) at dosages of 4 or 40 mg/kg/day (2 and 20 times the clinical usage) on days 6 through 15 of gestation. Untreated, vehicle and sham control groups were also incorporated into the study protocol. No meaningful differences were observed between the treated and control groups in maternal toxicity, gross and microscopic appearance of vagina, maternal reproductive parameters, fetal toxicity, and the incidence of visceral and skeletal malformations.