title: Ocular topotecan pharmacokinetics following topical administration to rabbits for diffused anterior retinoblastoma.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors: Unidad de Farmacocinética Clínica, Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Buenos Aires, Argentina.
authors: Paula
authors: P
authors: Taich
authors: Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Buenos Aires, Argentina.|Laboratorio de Farmacología, CIVETAN-CONICET, Facultad de Veterinaria, Universidad Nacional del Centro de la Provincia de Buenos Aires, Tandil, Argentina.
authors: Maria
authors: M
authors: Del Sole
authors: Servicio de Farmacia, Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina.
authors: Fabian
authors: F
authors: Buontempo
authors: Bioterio, Area de Laboratorio, Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina.
authors: Gustavo
authors: G
authors: Williams
authors: Unidad de Farmacocinética Clínica, Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Buenos Aires, Argentina.
authors: Ursula
authors: U
authors: Winter
authors: Servicios de Oftalmología y Hematología-Oncología, Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina.
authors: Mariana
authors: M
authors: Sgroi
authors: Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Buenos Aires, Argentina.|Servicios de Oftalmología y Hematología-Oncología, Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina.
authors: Guillermo
authors: G
authors: Chantada
authors: Unidad de Farmacocinética Clínica, Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina.|Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Buenos Aires, Argentina.
authors: Paula
authors: P
authors: Schaiquevich
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects; D003315:Cornea / Q000187:drug effects; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011817:Rabbits; D012175:Retinoblastoma / Q000188:drug therapy*; D014018:Tissue Distribution; D019772:Topotecan / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000187:drug effects*
chemical_list: D009883:Ophthalmic Solutions; D019772:Topotecan
keywords: aqueous humor; pharmacokinetics; rabbits; retinoblastoma; topotecan