Pharmacokinetic Analysis of Topotecan After Superselective Ophthalmic Artery Infusion and Periocular Administration in a Porcine Model

In Brief Purpose To characterize the vitreous and plasma pharmacokinetics of topotecan after ophthalmic artery infusion (OAI) subsequent to superselective artery catheterization and to compare it with periocular injection (POI). Methods The ophthalmic artery of 4 pigs was catheterized and 1 mg of topotecan infused over a period of 30 minutes. The contralateral eye was subsequently used for administering topotecan by POI. Serial vitreous specimens were obtained by microdialysis and plasma samples collected and assayed for total and lactone topotecan. Results Maximum total topotecan concentration in the vitreous (median, range) was significantly higher after OAI compared with POI (131.8 ng/mL [112.9–138.7] vs. 13.6 ng/mL [5.5–15.3], respectively; P < 0.005). Median vitreous exposure calculated as area under the curve for total topotecan attained after OAI was significantly higher than after POI (299.8 ng·hour/mL [247.6–347.2] and 48.9 ng·hour/mL [11.8–63.4], respectively; P < 0.05). The vitreous to plasma exposure ratio was 29 after OAI and 3.4 after POI. Systemic exposure for total topotecan was low after both modalities of administration, with a trend to be lower after OAI compared with POI (10.6 ng·hour/mL [6.8–13.4] vs. 18.7 ng·hour/mL [6.3–21.7]; P = 0.54). Conclusion Superselective OAI resulted in significantly higher vitreous concentrations and exposure and a trend toward lower systemic exposure than POI. Topotecan pharmacokinetics after superselective ophthalmic artery infusion was studied in a porcine model and compared with periocular administration as an alternative route for administration in retinoblastoma. Ophthalmic artery infusion of topotecan results in significantly higher vitreous exposure compared with periocular administration. Systemic exposure was low after both routes of administration.