Topotecan Penetrates Rabbit Vitreous After Systemic Administration

Abstract

Abstract: : Purpose: Topotecan is an inhibitor of DNA topoisomerase I that may have a role in the treatment of advanced retinoblastoma. Its ocular pharmacokinetics have not been described. The purpose of this study was to evaluate the vitreal pharmacokinetics of intravenously injected topotecan Methods: New Zealand White rabbits were given intravenous infusions of 0.25 mg/kg Topotecan over 4 minutes. Serial vitreal samples were obtained through pars plana vitreal taps, with simultaneous blood sampling. Topotecan plasma and vitreous concentrations were measured using HPLC. Results: The plasma disposition of topotecan in rabbits was similar to that measured in other species with a plasma clearance of 9.2 L/h/m² and terminal half life of 1.2 h. At the dosage administered, the area under the concentration-time curve (AUC_0-6) was 88 ng/ml*h. The vitreal topotecan disposition showed a clearance of 30.9 L/h/m² and a half life of 2.1 h. The AUC_0-6 in the vitreous was 22 ng/ml*h. Based upon the ratio of vitreous to plasma AUC, topotecan penetration into the vitreous was approximately 40%. Conclusions: Our results indicate that topotecan has a relatively high penetration into the vitreous. To that effect, the rabbit is a good model to study vitreal pharmacokinetics of topotecan.

Keywords: retinoblastoma • pharmacology