title: Retinal toxicity and ocular kinetics of 1-beta-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.
authors.affiliation: Department of Ophthalmology, Kanazawa University School of Medicine, Ishikawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mochizuki
authors.forename: M
authors.initials: M
authors.lastname: Torisaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Komatsu
authors.forename: T
authors.initials: T
authors.lastname: Tanahashi
authors.forename: K
authors.initials: K
authors.lastname: Ijichi
authors.forename: H
authors.initials: H
authors.lastname: Machida
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000633:toxicity*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D004596:Electroretinography / Q000187:drug effects; D005123:Eye / Q000378:metabolism*; D006207:Half-Life; D007267:Injections; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C031368:sorivudine