Artículo
Pharmacokinetics of Orbital Topotecan After Ophthalmic Artery Chemosurgery and Intravenous Infusion in the Swine Model
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
Fecha de publicación:
09/2023
Editorial:
Association for Research in Vision and Ophthalmology Inc.
Revista:
Investigative Ophthalmology and Visual Science
e-ISSN:
1552-5783
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
PHARMACOKINETICS
,
INTRAVITREAL
,
TOPOTECAN
,
RETINOBLASTOMA
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Colecciones
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
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
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