Pharmacokinetic analysis of topotecan after intra-vitreal injection. Implications for retinoblastoma treatment
| Autor: | Adriana Fandiño, Elliot Navo, Paula Schaiquevich, Christian Höcht, Guillermo F. Bramuglia, Guillermo L. Chantada, David H. Abramson, Emiliano Buitrago |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Drug
endocrine system diseases genetic structures Retinal Neoplasms media_common.quotation_subject Biological Availability Antineoplastic Agents Topotecan Lactone Aqueous humor Pharmacology Injections Aqueous Humor Cellular and Molecular Neuroscience Pharmacokinetics medicine Animals Chromatography High Pressure Liquid media_common Vitreous seeds Retinoblastoma Chemistry medicine.disease eye diseases Sensory Systems Pharmacokinetic analysis Vitreous Body Ophthalmology Topotecan Rabbits sense organs medicine.drug |
| Zdroj: | Experimental Eye Research. 91:9-14 |
| ISSN: | 0014-4835 |
| DOI: | 10.1016/j.exer.2010.03.009 |
| Popis: | Topotecan is a promising drug with activity against retinoblastoma, however, attaining therapeutic concentrations in the vitreous humor is still a challenge for the treatment of vitreous seeds in retinoblastoma. Our aim was to characterize topotecan pharmacokinetics in vitreous and aqueous humor, and to assess the systemic exposure after intra-vitreal injection in rabbits as an alternative route for maximizing local drug exposure. Anesthetized rabbits were administered intra-vitreal injections of 5 microg of topotecan. Vitreous, aqueous, and blood samples were collected at pre-defined time points. A validated high-performance liquid chromatography assay was used to quantitate topotecan (lactone and carboxylate) concentrations. Topotecan pharmacokinetic parameters were determined in vitreous, aqueous and plasma using a compartmental analysis. Topotecan lactone concentrations in the vitreous of the injected eye were about 8 ng/mL 48 h after drug administration. The median maximum vitreous, aqueous and plasma total topotecan concentrations (C(max)) were 5.3, 0.68 and 0.21 microg/mL, respectively. The C(max) vitreous/aqueous of treated eyes and the C(max) vitreous/plasma were approximately 8 and 254, respectively. Total topotecan exposure (AUC) in the vitreous of the injected eye was 50 times greater than the total systemic exposure. These findings suggest that intra-vitreal administration of only 5 microg of topotecan reaches significant local levels over an extended period of time while minimizing systemic exposure in the rabbit. Intra-vitreal topotecan administration offers a promising alternative route for enhanced drug exposure in the vitreous humor with potential application for treatment of vitreal seeds in retinoblastoma while avoiding systemic toxicities. |
| Databáze: | OpenAIRE |
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