title: BCNU in silicone oil in proliferative vitreoretinopathy: I. Solubility, stability (in vitro and in vivo), and antiproliferative (in vitro) studies.
abstract: Various pharmacologic agents have been tried to control proliferative vitreoretinopathy (PVR). However, most are water soluble and cannot be used with silicone oil (SO), a tamponade agent also used in PVR management. We evaluated a lipophilic, antiproliferative drug, BCNU, in regard to its solubility and stability in SO, its release from SO into an aqueous solution, and its effect on cell cultures. BCNU is soluble in SO (peak concentration in micrograms/ml 1020, 750, and 294 at 37 degrees C, 21 degrees C, and 4 degrees C, respectively), and stable (half-life = 6.7 weeks at 37 degrees C, 17.9 weeks at 21 degrees C). At 4 degrees C, no significant decrease in concentration up to eight weeks was noted. BCNU is released from SO to water (partition coefficient = 10.28 +/- 2.16). Its median inhibitory doses (ID50) on bovine retinal pigment epithelial (RPE), rabbit RPE, and subconjunctival fibroblast cells are 13, 1.9, and 15.6 micrograms/ml, respectively. BCNU may be a useful pharmacologic tool to control PVR.
authors.affiliation: Eye Research Institute of Retina Foundation, Boston, MA 02114.
authors.forename: H
authors.initials: H
authors.lastname: Chung
authors.forename: F I
authors.initials: FI
authors.lastname: Tolentino
authors.forename: V N
authors.initials: VN
authors.lastname: Cajita
authors.forename: N
authors.initials: N
authors.lastname: Ueno
authors.forename: M F
authors.initials: MF
authors.lastname: Refojo
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000032:analysis; D002330:Carmustine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004355:Drug Stability; D005128:Eye Diseases / Q000188:drug therapy*; D010857:Pigment Epithelium of Eye / Q000187:drug effects; D012164:Retinal Diseases / Q000188:drug therapy*; D012827:Silicone Oils; D012995:Solubility; D013997:Time Factors; D014822:Vitreous Body / Q000378:metabolism*; D014867:Water
chemical_list: D012827:Silicone Oils; D014867:Water; D002330:Carmustine