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  • Title: Pharmacokinetics of bevacizumab and its effect on vascular endothelial growth factor after intravitreal injection of bevacizumab in macaque eyes.
    Author: Miyake T, Sawada O, Kakinoki M, Sawada T, Kawamura H, Ogasawara K, Ohji M.
    Journal: Invest Ophthalmol Vis Sci; 2010 Mar; 51(3):1606-8. PubMed ID: 19875666.
    Abstract:
    PURPOSE: To evaluate the pharmacokinetics of intravitreally injected bevacizumab in the systemic circulation and the aqueous humor and its effect on vascular endothelial growth factor (VEGF) in the aqueous humor. METHODS: Bevacizumab (1.25 mg/50 microL) was injected into the vitreous cavity of the right eyes of three cynomolgus macaques. Aqueous humor and serum were obtained from the macaques just before injection and on days 1, 3, and 7 and weeks 2, 4, 6, and 8 after injection. The bevacizumab and VEGF concentrations were measured using enzyme-linked immunosorbent assay. RESULTS: Aqueous VEGF concentrations ranged from 63.2 to 106 pg/mL (mean, 80.0 +/- 22.6 pg/mL) before injection; decreased to <31.2 pg/mL, the lower limit of detection, in all eyes between 1 and 28 days after injection; and returned to the preinjection concentration at 42 days. Aqueous VEGF concentrations in the fellow eyes did not change throughout the experiment. Aqueous bevacizumab concentrations in the treated eyes reached a mean peak concentration of 49,500 +/- 10,900 ng/mL the day after injection and gradually declined, whereas those in the untreated eyes peaked at 3 days, with a mean concentration of 18.5 +/- 25.5 ng/mL, and declined to below 0.156 ng/mL, the limit of detection at 2 weeks. A maximum mean bevacizumab concentration of 1430 +/- 186 ng/mL was achieved in the serum 1 week after injection. CONCLUSIONS: Intravitreal injection of bevacizumab decreased the VEGF concentration in the treated eyes for at least 4 weeks and had no or a minimal effect on the untreated fellow eyes.
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