Retinal toxicity and ocular kinetics of 1-β-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil in rabbits

Abstract

The intraocular penetration of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU), a new antiviral drug, after oral administration, the effects of non-toxic intravitreal doses of BV-araU, and the intraocular kinetics of BV-araU after intraocular injection were studied in rabbits. The intravitreal penetration of BV-araU after oral administration was very poor: 0.11 +/- 0.13 micrograms/ml and 0.20 +/- 0.02 microgram/ml respectively in albino and pigmented rabbits 2 h after 30 mg/kg. An intravitreal injection of 200 micrograms BV-araU caused transient electroretinographic (ERG) changes, whereas a 100-micrograms injection and intravitreal irrigation with 20 micrograms/ml BV-araU caused no ERG and histologic changes over the 4-week follow-up period. The half-life of the intravitreal concentration of BV-araU after an intravitreal injection was short (2.4 h). The results suggest that an intravitreal injection of 100 micrograms BV-araU or an intravitreal irrigating solution containing 20 micrograms/ml BV-araU is non-toxic to the retina and may be used for treatment of retinitis caused by varicella-zoster virus or herpes simplex virus type 1.