Abstract
Purpose: :
To evaluate the pharmacokinetics of intravitreally injected bevacizumab and its effect on vascular endothelial growth factor (VEGF) in the aqueous humor of vitrectomized Macaque eyes
Methods: :
Three eyes of three cynomolgus macaques underwent standard pars plana vitrectomy and lensectomy. Macaques were allowed to recover for a minimum of 3 months before entering the study. Bevacizumab (1.25 mg/50 µl) was injected into the vitreous cavity of the vitrectomized eyes of three macaques. Aqueous humor were obtained from the macaques just before injection and on days 1, 3, and 7, and weeks 2, 4, 6, 8 after the injection. The bevacizumab and VEGF concentrations were measured using enzyme-linked immunosorbent assay.
Results: :
Aqueous bevacizumab concentrations in the vitrectomized eyes reached a mean peak concentration of 15,900 + 2,700 ng/ml the day after the injection and gradually declined. The half-life of 1.25 mg of intravitreally injected bevacizumab was 1.1 + 0.15 days (n=3; range 0.96-1.26) in the aqueous humor while it was 2.8 + 0.6days in the non-vitrectomized eyes in the previous study (Miyake, et al IOVS 2010). The aqueous VEGF concentrations ranged from 20.7 to 67.2 pg/ml (mean, 40.9 ± 23.8 pg/ml) before the injection and decreased to less than 6.0 pg/ml, the lower limit of detection, in all eyes between 1 and 7 days after the injection. Aqueous VEGF returned to a detectable level at 2 weeks in two eyes and at 4 weeks in the other eye while the decreased level of VEGF lasted for 4-6 weeks in the non-vitrectomized eyes in the previous study. The aqueous VEGF concentrations in the fellow eyes did not change throughout the experiment.
Conclusions: :
The half-life of the intravitreally injected bevacizumab in the vitrectomized eyes reduced by 60% compared with non-vitrectomized eyes. The effect of intraviterally injected bevacizumab on the concentration of aqueous VEGF lasted much less in the vitrectomized eyes compared with in non-vitrectomized eyes.
Keywords: vascular endothelial growth factor • aqueous • injection