Clearance of antitransferrin receptor immunotoxin from the rabbit eye.
PURPOSE: Antitransferrin receptor immunotoxin has potent antiproliferative effects on proliferating human ocular cells in vitro, and shows promise in the treatment of ocular proliferative diseases, such as proliferative vitreoretinopathy, bleb scarring after trabeculectomy, or corneal epithelial downgrowth syndrome. Before treating patients, the pharmacokinetics of immunotoxin must be known. The purpose of this study was to determine the clearance of antitransferrin receptor immunotoxin from the rabbit eye after ocular injection. METHODS: Immunotoxin (1,000 ng/0.1 ml PBS) was injected into the vitreous cavity of gas vitrectomized rabbit eyes. Immunotoxin in aqueous, vitreous, and plasma was measured by ELISA at various times after injection. Similar measurements were obtained after immunotoxin was injected into the anterior chamber or subconjunctival space of eyes which had not received vitrectomy. Cultured human retinal pigment epithelial cells were exposed to vitreous fluid obtained after intravitreal injection, and counted after four days, to determine the bioactivity of immunotoxin recovered from vitreous samples. RESULTS: Immunotoxin was cleared rapidly from the vitreous cavity over the first 24 hr (t1/2 = 8.0 hr), and thereafter was slow. Drug recovered from the vitreous cavity retained significant antiproliferative activity at 96 hr. Immunotoxin was cleared within 6 hr from the aqueous after anterior chamber injection, and was not present inside the eye after subconjunctival injection. The plasma did not contain immunotoxin after any of these injections. CONCLUSIONS: The favorable pharmacokinetics of antitransferrin receptor immunotoxin in the rabbit eye suggests that it could be useful in the treatment of ocular proliferative disorders.
Handa, JT; Pearson, A; Jaffe, GJ
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