Intraocular Pharmacokinetics of Ranibizumab in Vitrectomized Versus Nonvitrectomized Eyes

Abstract

Overall intraocular pharmacokinetic properties of ranibizumab in vitrectomized eyes were similar to those in nonvitrectomized eyes. Our data do not support the use of different dosing regimens of ranibizumab in vitrectomized eyes.

Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model

“…Previous studies suggest the half-life of intravitreally administered drugs may be proportional to their molecular size. 11,18 The half-life of VEGF-Trap (145 kDa) was estimated to be 4 days, similar to the estimates in our study, based on the half-life of ranibizumab (48 kDa), 14,16,19 bevacizumab (149 kDa), 13,17,20,21 and rituximab (145 kDa). 22 In addition, we could directly compare the PK parameters for ranibizumab, bevacizumab, and VEGF-Trap, because we had conducted the PK studies for these three anti-VEGF agents using the same experimental methodologies.…”

“…The vitreous half-life for ranibizumab, bevacizumab, and VEGF-Trap were 2.75, 7.06, and 3.63 days, respectively. 13,14 The elimination of vitreous bevacizumab consisted of two distinct phases, fitting well to the two-compartment model. Thus, the comparison of MRTs between these three anti-VEGF agents, rather than their half-lives, provides more accurate insights.…”

“…The intraocular PK of intravitreally injected VEGF-Trap was assessed by the same experimental design used in our previous studies. 13,14 Briefly, the animals were anesthetized with an intramuscular injection of 15 mg/kg of Zoletil anesthesia (1% proparacaine hydrochloride ophthalmic eye drops; Alcaine; Alcon Laboratories Inc., Fort Worth, TX, USA) was administered after dilation of the eyes with phenylephrine hydrochloride and tropicamide eye drops (Mydrin-P; Santen Pharmaceutical Co., Osaka, Japan). After placing 5% povidone iodine on the periocular region and the conjunctiva of the right eye, VEGF-Trap (0.3 mg/0.03 ml) was intravitreally administered to the right eye 1 mm behind the surgical limbus in the superiotemporal quadrant by injection with a 30-gauge needle and a Hamilton syringe (Hamilton Company, Reno, NV, USA).…”

“…13,14,16 Briefly, the 165 amino-acid variants of human recombinant VEGF (rVEGF) was immobilized on 96-well flat-bottom plates (Corning Inc., Corning, NY, USA). The human rVEGF was diluted to 1.0 mg/ml in 50 mM carbonate buffer (pH 9) and then aliquoted onto the 96-well plates (100 ml per well).…”

“…This model was previously used for the study of intraocular PK properties of intravitreally injected bevacizumab and ranibizumab. 13,14 In addition, we assessed the differences in the PK properties and bioavailability of bevacizumab, ranibizumab, and VEGFTrap by comparing our current results with the data from our previous studies. 13,14 Materials and methods…”