Intraocular concentrations of chemotherapeutic agents after systemic or local administration

Objectives: To investigate the concentrations of carboplatin and etoposide achieved in the aqueous and vitreous humors after intravenous infusion in nonhuman primates, and to investigate whether local administration of carboplatin might result in higher concentrations in the vitreous humor. Methods: Macaca fascicularis primates were treated with 1 of 3 regimens: (1) intravenous carboplatin (18.7 mg/kg), etoposide (5 mg/kg), and vincristine sulfate (0.05 mg/kg), (2) peribulbar carboplatin(10 mg/mL), or (3) episcleral balloon carboplatin(10 mg/mL). Concentrations of chemotherapeutic agents were measured in the plasma and in the aqueous and vitreous humors. Results: No measurable amount of etoposide was detected in the aqueous or vitreous humor after intravenous administration. Mean measured peak vitreous concentration of carboplatin after intravenous administration was 0.31 mu g/mL, which was 1% of the peak plasma value. Mean measured peak vitreous concentrations of carboplatin after peribulbar or episcleral balloon administration were 2.38 mu g/mL and 2.95 mu g/mL, respectively, which represent 7.68- and 9.52-fold increases over the concentration achieved after intravenous administration. No serious toxic effect was observed in any animal. Conclusions: Peribulbar and episcleral balloon administration of carboplatin seemed to be safe and resulted in higher vitreous concentrations than intravenous administration in this model. These results suggest that these alternate routes of delivery should be explored in children with vitreous seeding of retinoblastoma.