PURPOSE: The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys. METHODS: Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the pharmacokinetics and toxicological properties of NX1838 were determined following six biweekly bilateral injections of 0.25 or 0.50 mg/eye or following four biweekly bilateral injections of 0.10 mg per eye followed by two biweekly bilateral injections of 1.0 mg per eye. RESULTS: Plasma and vitreous humor NX1838 concentrations were linearly related to the dose administered. NX1838 was cleared intact from the vitreous humor into the plasma with a half-life of approximately 94 h, which was in agreement with the plasma terminal half-life. Vascular endothelial growth factor (VEGF)-binding assays demonstrated that the NX1838 remaining in the vitreous humor after 28 days was fully active. No toxicological effects or antibody responses were evident. CONCLUSIONS: The no observable effect level was greater than six biweekly bilateral 0.50 mg/eye doses or two biweekly bilateral 1.0 mg/eye doses. These pharmacokinetic and safety data support monthly 1 or 2 mg/eye dose regimens in human clinical trials.
PURPOSE: The objective of this study was to determine the pharmacokinetics and safety for NX1838 following injection into the vitreous humor of rhesus monkeys. METHODS: Plasma and vitreous humor pharmacokinetics were determined following a single bilateral 0.25, 0.50, 1.0, 1.5, or 2.0 mg/eye dose. In addition, the pharmacokinetics and toxicological properties of NX1838 were determined following six biweekly bilateral injections of 0.25 or 0.50 mg/eye or following four biweekly bilateral injections of 0.10 mg per eye followed by two biweekly bilateral injections of 1.0 mg per eye. RESULTS: Plasma and vitreous humor NX1838 concentrations were linearly related to the dose administered. NX1838 was cleared intact from the vitreous humor into the plasma with a half-life of approximately 94 h, which was in agreement with the plasma terminal half-life. Vascular endothelial growth factor (VEGF)-binding assays demonstrated that the NX1838 remaining in the vitreous humor after 28 days was fully active. No toxicological effects or antibody responses were evident. CONCLUSIONS: The no observable effect level was greater than six biweekly bilateral 0.50 mg/eye doses or two biweekly bilateral 1.0 mg/eye doses. These pharmacokinetic and safety data support monthly 1 or 2 mg/eye dose regimens in human clinical trials.
Authors: M C Willis; B D Collins; T Zhang; L S Green; D P Sebesta; C Bell; E Kellogg; S C Gill; A Magallanez; S Knauer; R A Bendele; P S Gill; N Janjić; B Collins Journal: Bioconjug Chem Date: 1998 Sep-Oct Impact factor: 4.774
Authors: J Mordenti; R A Cuthbertson; N Ferrara; K Thomsen; L Berleau; V Licko; P C Allen; C R Valverde; Y G Meng; D T Fei; K M Fourre; A M Ryan Journal: Toxicol Pathol Date: 1999 Sep-Oct Impact factor: 1.902
Authors: D Jellinek; L S Green; C Bell; C K Lynott; N Gill; C Vargeese; G Kirschenheuter; D P McGee; P Abesinghe; W A Pieken Journal: Biochemistry Date: 1995-09-12 Impact factor: 3.162
Authors: Lihteh Wu; María A Martínez-Castellanos; Hugo Quiroz-Mercado; J Fernando Arevalo; María H Berrocal; Michel E Farah; Mauricio Maia; José A Roca; Francisco J Rodriguez Journal: Graefes Arch Clin Exp Ophthalmol Date: 2007-08-03 Impact factor: 3.117