Pharmacokinetics of Melphalan After Intravitreal Injection in a Rabbit Model.

Abstract Purpose: Although widely used for vitreous seed control in retinoblastoma patients, currently there are no data on melphalan pharmacokinetics after intravitreal injections. Therefore, in this study, we characterized the ocular and systemic disposition of melphalan after intravitreal injection in the rabbit eye. Methods: New Zealand rabbits received a single intravitreal injection of 15 μg of melphalan. Vitreous, aqueous, retina, and blood samples were collected at different times up to 12 h after the injection. Melphalan was quantitated in the biological samples using a validated high-performance liquid-chromatography technique and pharmacokinetic parameters were calculated by means of compartmental models. Results: Model-predicted melphalan maximum vitreous, aqueous, and retina concentrations were 7.8 μg/mL, 0.024 μg/mL, and 9.8 μg/g tissue, respectively, attained immediately and at 0.8 and 0.25 h after intravitreal injection. Melphalan vitreous concentrations were higher than 0.3 μg/mL for 5 h ...