Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma

Autores
Taich, Paula Juliana; del Sole, Maria Jose; Buontempo, Fabian; Williams, Gustavo; Winter, Ursula Andrea; Sgroi, Mariana; Chantada, Guillermo Luis; Schaiquevich, Paula Susana
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objectives: We characterized and compared the in-vivo absorption of topotecan into the aqueous humor after instillation of aqueous and ointment formulations. Methods: A lanolin/petrolatum ointment was used. New Zealand rabbits were instilled with topotecan solution (6 μg, group A), a single 10 μg dose of topotecan ointment (group B) or with five 10 μg doses of topotecan ointment (group C). Aqueous humor samples were collected at different times. Corneal samples were collected only for group A. Topotecan was quantified using HPLC, and pharmacokinetic parameters were calculated. Acute corneal epithelial toxicity was assessed after multiple instillations of topotecan ointment. Key findings: Total topotecan maximum aqueous humor concentration (Cmax) was 16.1, 69.9 and 287 ng/ml in group A, B and C, respectively. A single dose of topotecan ointment increased threefold and sevenfold the aqueous humor Cmax, and exposure compared to the aqueous formulation. Aqueous humor concentrations from group C eyes were substantially above the cytotoxic concentration for retinoblastoma cells. No corneal toxicity was evident after ointment instillation. Conclusions: Topotecan penetrated into the aqueous humor of the rabbit eye after multiple doses of an ointment in concentrations pharmacologically active against retinoblastoma cells without eliciting acute toxicity. Topotecan ointment may translate to the clinical treatment of anterior segment disseminated retinoblastoma.
Fil: Taich, Paula Juliana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: del Sole, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Buontempo, Fabian. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Williams, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sgroi, Mariana. 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. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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
Aqueous Humor
Pharmacokinetics
Rabbits
Retinoblastoma
Topotecan
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/58496
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/58496
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastomaTaich, Paula Julianadel Sole, Maria JoseBuontempo, FabianWilliams, GustavoWinter, Ursula AndreaSgroi, MarianaChantada, Guillermo LuisSchaiquevich, Paula SusanaAqueous HumorPharmacokineticsRabbitsRetinoblastomaTopotecanhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Objectives: We characterized and compared the in-vivo absorption of topotecan into the aqueous humor after instillation of aqueous and ointment formulations. Methods: A lanolin/petrolatum ointment was used. New Zealand rabbits were instilled with topotecan solution (6 μg, group A), a single 10 μg dose of topotecan ointment (group B) or with five 10 μg doses of topotecan ointment (group C). Aqueous humor samples were collected at different times. Corneal samples were collected only for group A. Topotecan was quantified using HPLC, and pharmacokinetic parameters were calculated. Acute corneal epithelial toxicity was assessed after multiple instillations of topotecan ointment. Key findings: Total topotecan maximum aqueous humor concentration (Cmax) was 16.1, 69.9 and 287 ng/ml in group A, B and C, respectively. A single dose of topotecan ointment increased threefold and sevenfold the aqueous humor Cmax, and exposure compared to the aqueous formulation. Aqueous humor concentrations from group C eyes were substantially above the cytotoxic concentration for retinoblastoma cells. No corneal toxicity was evident after ointment instillation. Conclusions: Topotecan penetrated into the aqueous humor of the rabbit eye after multiple doses of an ointment in concentrations pharmacologically active against retinoblastoma cells without eliciting acute toxicity. Topotecan ointment may translate to the clinical treatment of anterior segment disseminated retinoblastoma.Fil: Taich, Paula Juliana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: del Sole, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Buontempo, Fabian. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Williams, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sgroi, Mariana. 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. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schaiquevich, Paula Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaPharmaceutical Press-Royal Pharmaceutical Society Great Britian2017-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/58496Taich, Paula Juliana; del Sole, Maria Jose; Buontempo, Fabian; Williams, Gustavo; Winter, Ursula Andrea; et al.; Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma; Pharmaceutical Press-Royal Pharmaceutical Society Great Britian; Journal of Pharmacy and Pharmacology; 69; 5; 5-2017; 574-5810022-3573CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/jphp.12624info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.12624info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:01Zoai:ri.conicet.gov.ar:11336/58496instacron: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 09:45:01.802CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma
title Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma
spellingShingle Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma
Taich, Paula Juliana
Aqueous Humor
Pharmacokinetics
Rabbits
Retinoblastoma
Topotecan
title_short Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma
title_full Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma
title_fullStr Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma
title_full_unstemmed Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma
title_sort Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma
dc.creator.none.fl_str_mv Taich, Paula Juliana
del Sole, Maria Jose
Buontempo, Fabian
Williams, Gustavo
Winter, Ursula Andrea
Sgroi, Mariana
Chantada, Guillermo Luis
Schaiquevich, Paula Susana
author Taich, Paula Juliana
author_facet Taich, Paula Juliana
del Sole, Maria Jose
Buontempo, Fabian
Williams, Gustavo
Winter, Ursula Andrea
Sgroi, Mariana
Chantada, Guillermo Luis
Schaiquevich, Paula Susana
author_role author
author2 del Sole, Maria Jose
Buontempo, Fabian
Williams, Gustavo
Winter, Ursula Andrea
Sgroi, Mariana
Chantada, Guillermo Luis
Schaiquevich, Paula Susana
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aqueous Humor
Pharmacokinetics
Rabbits
Retinoblastoma
Topotecan
topic Aqueous Humor
Pharmacokinetics
Rabbits
Retinoblastoma
Topotecan
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objectives: We characterized and compared the in-vivo absorption of topotecan into the aqueous humor after instillation of aqueous and ointment formulations. Methods: A lanolin/petrolatum ointment was used. New Zealand rabbits were instilled with topotecan solution (6 μg, group A), a single 10 μg dose of topotecan ointment (group B) or with five 10 μg doses of topotecan ointment (group C). Aqueous humor samples were collected at different times. Corneal samples were collected only for group A. Topotecan was quantified using HPLC, and pharmacokinetic parameters were calculated. Acute corneal epithelial toxicity was assessed after multiple instillations of topotecan ointment. Key findings: Total topotecan maximum aqueous humor concentration (Cmax) was 16.1, 69.9 and 287 ng/ml in group A, B and C, respectively. A single dose of topotecan ointment increased threefold and sevenfold the aqueous humor Cmax, and exposure compared to the aqueous formulation. Aqueous humor concentrations from group C eyes were substantially above the cytotoxic concentration for retinoblastoma cells. No corneal toxicity was evident after ointment instillation. Conclusions: Topotecan penetrated into the aqueous humor of the rabbit eye after multiple doses of an ointment in concentrations pharmacologically active against retinoblastoma cells without eliciting acute toxicity. Topotecan ointment may translate to the clinical treatment of anterior segment disseminated retinoblastoma.
Fil: Taich, Paula Juliana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: del Sole, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Buontempo, Fabian. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Williams, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Winter, Ursula Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sgroi, Mariana. 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. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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 Objectives: We characterized and compared the in-vivo absorption of topotecan into the aqueous humor after instillation of aqueous and ointment formulations. Methods: A lanolin/petrolatum ointment was used. New Zealand rabbits were instilled with topotecan solution (6 μg, group A), a single 10 μg dose of topotecan ointment (group B) or with five 10 μg doses of topotecan ointment (group C). Aqueous humor samples were collected at different times. Corneal samples were collected only for group A. Topotecan was quantified using HPLC, and pharmacokinetic parameters were calculated. Acute corneal epithelial toxicity was assessed after multiple instillations of topotecan ointment. Key findings: Total topotecan maximum aqueous humor concentration (Cmax) was 16.1, 69.9 and 287 ng/ml in group A, B and C, respectively. A single dose of topotecan ointment increased threefold and sevenfold the aqueous humor Cmax, and exposure compared to the aqueous formulation. Aqueous humor concentrations from group C eyes were substantially above the cytotoxic concentration for retinoblastoma cells. No corneal toxicity was evident after ointment instillation. Conclusions: Topotecan penetrated into the aqueous humor of the rabbit eye after multiple doses of an ointment in concentrations pharmacologically active against retinoblastoma cells without eliciting acute toxicity. Topotecan ointment may translate to the clinical treatment of anterior segment disseminated retinoblastoma.
publishDate 2017
dc.date.none.fl_str_mv 2017-05
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/11336/58496
Taich, Paula Juliana; del Sole, Maria Jose; Buontempo, Fabian; Williams, Gustavo; Winter, Ursula Andrea; et al.; Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma; Pharmaceutical Press-Royal Pharmaceutical Society Great Britian; Journal of Pharmacy and Pharmacology; 69; 5; 5-2017; 574-581
0022-3573
CONICET Digital
CONICET
url http://hdl.handle.net/11336/58496
identifier_str_mv Taich, Paula Juliana; del Sole, Maria Jose; Buontempo, Fabian; Williams, Gustavo; Winter, Ursula Andrea; et al.; Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma; Pharmaceutical Press-Royal Pharmaceutical Society Great Britian; Journal of Pharmacy and Pharmacology; 69; 5; 5-2017; 574-581
0022-3573
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/jphp.12624
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.12624
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pharmaceutical Press-Royal Pharmaceutical Society Great Britian
publisher.none.fl_str_mv Pharmaceutical Press-Royal Pharmaceutical Society Great Britian
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)
instname_str 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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score 13.13397

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