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dc.contributor.author
Buitrago, Emiliano
dc.contributor.author
Höcht, Christian
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Chantada, Guillermo Luis
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Fandiño, Adriana Cristina
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Navo, Elliot
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Abramson, David H.
dc.contributor.author
Schaiquevich, Paula Susana
dc.contributor.author
Bramuglia, Guillermo Federico
dc.date.available
2023-03-16T13:02:09Z
dc.date.issued
2010-07
dc.identifier.citation
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
dc.identifier.issn
0014-4835
dc.identifier.uri
http://hdl.handle.net/11336/190746
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Ltd - Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
RETINOBLASTOMA
dc.subject
TOPOTECAN
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PHARMACOKINETICS
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Farmacología y Farmacia
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Pharmacokinetic analysis of topotecan after intra-vitreal injection: implications for retinoblastoma treatment
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-03-15T10:05:16Z
dc.journal.volume
91
dc.journal.number
1
dc.journal.pagination
9-14
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Buitrago, Emiliano. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
dc.description.fil
Fil: Höcht, Christian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
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Fil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
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Fil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
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Fil: Navo, Elliot. Memorial Sloan-Kettering Cancer Center; Estados Unidos
dc.description.fil
Fil: Abramson, David H.. Memorial Sloan-Kettering Cancer Center; Estados Unidos
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Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Bramuglia, Guillermo Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
dc.journal.title
Experimental Eye Research
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0014483510000849
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.exer.2010.03.009
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