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dc.contributor.author
Requejo, Flavio
dc.contributor.author
Opezzo, Javier
dc.contributor.author
Vater, Alan
dc.contributor.author
Asprea, Marcelo
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Lagomarsino, Edmundo Dante
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Sampor, Claudia
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Fandiño, Adriana Cristina
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Chantada, Guillermo Luis
dc.contributor.author
Francis, Jasmine H.
dc.contributor.author
Abramson, David H.
dc.contributor.author
Schaiquevich, Paula Susana
dc.date.available
2024-06-04T11:51:46Z
dc.date.issued
2023-09
dc.identifier.citation
Requejo, Flavio; Opezzo, Javier; Vater, Alan; Asprea, Marcelo; Lagomarsino, Edmundo Dante; et al.; Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model; Association for Research in Vision and Ophthalmology Inc.; Investigative Ophthalmology and Visual Science; 64; 12; 9-2023; 1-6
dc.identifier.uri
http://hdl.handle.net/11336/236941
dc.description.abstract
Purpose: Surgery, multiagent systemic chemotherapy, and radiation are used for patients with orbital retinoblastoma but are associated with unacceptable short- and long-term toxicity (including death). We studied orbital and systemic exposure of topotecan in the swine model after ophthalmic artery chemosurgery (OAC) and intravenous (IV) delivery.Methods: Landrace pigs (n = 3) underwent 30-minute OAC of topotecan (4 mg), and samples were serially obtained from the femoral artery and from a microdialysis probe inserted into the lateral rectus muscle sheath of the infused eye as a surrogate of the orbital irrigation. Animals were recovered, and, after a wash-out period, plasma and microdialysate samples from the contralateral eye were collected after a 30-minute IV infusion of topotecan (4 mg). Samples were quantified by high-performance liquid chromatography, and population pharmacokinetic analysis was conducted using MonolixSuite.Results: After OAC, median topotecan exposure in the orbit was 5624 ng × h/mL (range 3922-12531) compared to 23 ng × h/mL (range 18-75) after IV infusion. Thus, topotecan exposure in the orbit was 218-fold (range 75-540) higher after OAC than after IV infusion despite comparable systemic exposure (AUCpl) between routes (AUCpl, OAC: 141 ng × h/mL [127-191] versus AUCpl, IV: 139 ng × h/mL [126-186]). OAC was more selective to target the orbit because the median (range) orbital-to-plasma exposure ratio was 44 (28-65) after OAC compared to 0.18 (0.13-0.40) after IV infusion.Conclusions: OAC of topotecan resulted in higher orbital exposure than after IV infusion and was a more selective route for local drug delivery. Patients with orbital retinoblastoma may benefit from a multimodal treatment strategy including OAC therapy.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Association for Research in Vision and Ophthalmology Inc.
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
PHARMACOKINETICS
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INTRAVITREAL
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TOPOTECAN
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RETINOBLASTOMA
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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
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2024-03-26T13:57:15Z
dc.identifier.eissn
1552-5783
dc.journal.volume
64
dc.journal.number
12
dc.journal.pagination
1-6
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Requejo, Flavio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
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Fil: Opezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Vater, Alan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Asprea, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Lagomarsino, Edmundo Dante. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
dc.description.fil
Fil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
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Fil: Chantada, Guillermo Luis. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Hospital Sant Joan de Deu Barcelona; España. Fundacion Perez-Scremini; Uruguay
dc.description.fil
Fil: Francis, Jasmine H.. Memorial Sloan Kettering Cancer Center; Estados Unidos. Cornell Medical School; Estados Unidos
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Fil: Abramson, David H.. Memorial Sloan Kettering Cancer Center; Estados Unidos. Cornell Medical School; Estados Unidos
dc.description.fil
Fil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Investigative Ophthalmology and Visual Science
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1167/iovs.64.12.3
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2792715
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