Artículo
Pharmacokinetic analysis of topotecan after intra-vitreal injection: implications for retinoblastoma treatment
Buitrago, Emiliano; Höcht, Christian; Chantada, Guillermo Luis
; Fandiño, Adriana Cristina; Navo, Elliot; Abramson, David H.; Schaiquevich, Paula Susana
; Bramuglia, Guillermo Federico
Fecha de publicación:
07/2010
Editorial:
Academic Press Ltd - Elsevier Science Ltd
Revista:
Experimental Eye Research
ISSN:
0014-4835
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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 μg 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 (Cmax) were 5.3, 0.68 and 0.21 μg/mL, respectively. The Cmax vitreous/aqueous of treated eyes and the Cmax 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 μg 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.
Palabras clave:
RETINOBLASTOMA
,
TOPOTECAN
,
PHARMACOKINETICS
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Identificadores
Colecciones
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Buitrago, Emiliano; Höcht, Christian; Chantada, Guillermo Luis; Fandiño, Adriana Cristina; Navo, Elliot; et al.; Pharmacokinetic analysis of topotecan after intra-vitreal injection: implications for retinoblastoma treatment; Academic Press Ltd - Elsevier Science Ltd; Experimental Eye Research; 91; 1; 7-2010; 9-14
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