Measurement of intraocular concentrations of etoposide after systemic and local administration

To determine and compare the concentrations of etoposide achieved in the aqueous and vitreous humors after intravenous and subconjunctival administration.

Eight New Zealand rabbits were treated with etoposide (5mg/kg) intravenous and etoposide (2.5 mg/ml, 0.5 ml) subconjunctival respectively. The samples of the aqueous and vitreous humors of rabbits were drawed at 1, 2, 3 hours after the end of infusion. The concentrations of the etoposide were determined by high-performance liquid chromatography. A Diamonsil TM C18 column ( 6 x 40 mm, 3 microm ) with a mobile phase of 400 ml of methanol and 600 ml of 100 mmol x L(-1) sodium dihydrogen phosphate with 0.02 mmol x L(-1) dioctyl sodium sulfosuccinate and 0.5% triethylanine (pH value was adjusted to 6 by phosphoric acid) was used. The detective wavelength was at 235 nm and the flow rate was 1.0 ml x min(-1).

The concentrations of etoposide in aqueous and vitreous humors after administrated in intravenous for 1, 2, 3 hours were 38.5, 52.2, 44.1(ng/ml) and 12.0, 25.1, 18.0 (ng/ml) respectively. The concentrations of etoposide in aqueous and vitreous humors after infused in subconjunctival for 1, 2, 3 hours were 98.0, 113.0, 99.0 (ng/ml) and 43.7, 66.7, 32.4 (ng/ml) respectively. The concentrations in the aqueous and vitreous humor after local administrated were 2 to 4 times higher than those obtained after intravenous administration. There are statistical significance between the concentrations of etoposide of aqueous and vitreous humor after intravenous and subconjunctival administration.

The delivery of subconjunctival of etoposide results in higher concentrations in aqueous and vitreous humors than intravenous administration. These results suggest that local administration of chemotherapeutic agents should be more effective for retinoblastoma chemotherapy than systemic administration.