Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model
- Autores
- Requejo, Flavio; Opezzo, Javier; Vater, Alan; Asprea, Marcelo; Lagomarsino, Edmundo Dante; Sampor, Claudia; Fandiño, Adriana Cristina; Chantada, Guillermo Luis; Francis, Jasmine H.; Abramson, David H.; Schaiquevich, Paula Susana
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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.
Fil: Requejo, Flavio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Opezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Vater, Alan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Asprea, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Lagomarsino, Edmundo Dante. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
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
Fil: Francis, Jasmine H.. Memorial Sloan Kettering Cancer Center; Estados Unidos. Cornell Medical School; Estados Unidos
Fil: Abramson, David H.. Memorial Sloan Kettering Cancer Center; Estados Unidos. Cornell Medical School; Estados Unidos
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 - Materia
-
PHARMACOKINETICS
INTRAVITREAL
TOPOTECAN
RETINOBLASTOMA - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/236941
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Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine ModelRequejo, FlavioOpezzo, JavierVater, AlanAsprea, MarceloLagomarsino, Edmundo DanteSampor, ClaudiaFandiño, Adriana CristinaChantada, Guillermo LuisFrancis, Jasmine H.Abramson, David H.Schaiquevich, Paula SusanaPHARMACOKINETICSINTRAVITREALTOPOTECANRETINOBLASTOMAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Purpose: 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.Fil: Requejo, Flavio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Opezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vater, Alan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Asprea, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Lagomarsino, Edmundo Dante. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: 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; UruguayFil: Francis, Jasmine H.. Memorial Sloan Kettering Cancer Center; Estados Unidos. Cornell Medical School; Estados UnidosFil: Abramson, David H.. Memorial Sloan Kettering Cancer Center; Estados Unidos. Cornell Medical School; Estados UnidosFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAssociation for Research in Vision and Ophthalmology Inc.2023-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/236941Requejo, 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; 1-61552-5783CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.64.12.3info:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2792715info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:02:01Zoai:ri.conicet.gov.ar:11336/236941instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:02:01.831CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model |
title |
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model |
spellingShingle |
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model Requejo, Flavio PHARMACOKINETICS INTRAVITREAL TOPOTECAN RETINOBLASTOMA |
title_short |
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model |
title_full |
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model |
title_fullStr |
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model |
title_full_unstemmed |
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model |
title_sort |
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model |
dc.creator.none.fl_str_mv |
Requejo, Flavio Opezzo, Javier Vater, Alan Asprea, Marcelo Lagomarsino, Edmundo Dante Sampor, Claudia Fandiño, Adriana Cristina Chantada, Guillermo Luis Francis, Jasmine H. Abramson, David H. Schaiquevich, Paula Susana |
author |
Requejo, Flavio |
author_facet |
Requejo, Flavio Opezzo, Javier Vater, Alan Asprea, Marcelo Lagomarsino, Edmundo Dante Sampor, Claudia Fandiño, Adriana Cristina Chantada, Guillermo Luis Francis, Jasmine H. Abramson, David H. Schaiquevich, Paula Susana |
author_role |
author |
author2 |
Opezzo, Javier Vater, Alan Asprea, Marcelo Lagomarsino, Edmundo Dante Sampor, Claudia Fandiño, Adriana Cristina Chantada, Guillermo Luis Francis, Jasmine H. Abramson, David H. Schaiquevich, Paula Susana |
author2_role |
author author author author author author author author author author |
dc.subject.none.fl_str_mv |
PHARMACOKINETICS INTRAVITREAL TOPOTECAN RETINOBLASTOMA |
topic |
PHARMACOKINETICS INTRAVITREAL TOPOTECAN RETINOBLASTOMA |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
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. Fil: Requejo, Flavio. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Opezzo, Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vater, Alan. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Asprea, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Lagomarsino, Edmundo Dante. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Sampor, Claudia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Fandiño, Adriana Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina 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 Fil: Francis, Jasmine H.. Memorial Sloan Kettering Cancer Center; Estados Unidos. Cornell Medical School; Estados Unidos Fil: Abramson, David H.. Memorial Sloan Kettering Cancer Center; Estados Unidos. Cornell Medical School; Estados Unidos 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 |
description |
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. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-09 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/236941 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 1552-5783 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/236941 |
identifier_str_mv |
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 1552-5783 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1167/iovs.64.12.3 info:eu-repo/semantics/altIdentifier/url/https://iovs.arvojournals.org/article.aspx?articleid=2792715 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Association for Research in Vision and Ophthalmology Inc. |
publisher.none.fl_str_mv |
Association for Research in Vision and Ophthalmology Inc. |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1842269731888824320 |
score |
13.13397 |