title: SCH 412499: biodistribution and safety of an adenovirus containing P21(WAF-1/CIP-1) following subconjunctival injection in Cynomolgus monkeys.
abstract: Monkey studies were conducted for the preclinical safety assessment of SCH 412499, an adenovirus encoding p21, administered by subconjunctival injection prior to trabeculectomy for postoperative maintenance of the surgical opening. Biodistribution of SCH 412499 was minimal and there was no systemic toxicity. Findings included swollen, partially closed or shut eye(s) and transient congestion in the conjunctiva. A mononuclear cell infiltrate was present in the conjunctiva, choroid and other ocular tissues, but completely or partially resolved over time. Electroretinograms and visual evoked potentials revealed no adverse findings. Thus, the findings are not expected to preclude the clinical investigation of SCH 412499.
authors.affiliation: Drug Safety, Schering-Plough Research Institute. Lafayette, New Jersey 07848-0032, USA. robert.veneziale@spcorp.com
authors.forename: Robert W
authors.initials: RW
authors.lastname: Veneziale
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Bral
authors.forename: Dinesh P
authors.initials: DP
authors.lastname: Sinha
authors.forename: Robert W
authors.initials: RW
authors.lastname: Watkins
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cartwright
authors.forename: Irwin Y
authors.initials: IY
authors.lastname: Rosenblum
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Treinen
authors.forename: Narendra S
authors.initials: NS
authors.lastname: Kishnani
authors.forename: Joyce
authors.initials: J
authors.lastname: Nelson
authors.forename: Zoe
authors.initials: Z
authors.lastname: Chen
authors.forename: Barbara
authors.initials: B
authors.lastname: Faha
authors.forename: D
authors.initials: D
authors.lastname: Maneval
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Munger
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Cai
authors.forename: Constance
authors.initials: C
authors.lastname: Cullen
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Arezzo
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003228:Conjunctiva; D003231:Conjunctivitis / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D005074:Evoked Potentials, Visual / Q000502:physiology; D005123:Eye / Q000473:pathology; D005260:Female; D015316:Genetic Therapy; D020327:Glaucoma Drainage Implants; D006339:Heart Rate / Q000502:physiology; D007267:Injections; D008252:Macaca fascicularis; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014129:Trabecular Meshwork; D014945:Wound Healing
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21