March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Clinical Pharmacokinetics Of Melphalan After Super-Selective Ophthalmic Artery Infusion In Children With Retinoblastoma
Author Affiliations & Notes
  • Paula J. Taich
    Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina
  • Emiliano Buitrago
    Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina
  • Andres Porta
    Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina
  • Alejandro Ceciliano
    Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina
  • Adriana Fandiño
    Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina
  • Claudia Sampor
    Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina
  • Guillermo Chantada
    Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina
  • Paula Schaiquevich
    Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina
  • Footnotes
    Commercial Relationships  Paula J. Taich, None; Emiliano Buitrago, None; Andres Porta, None; Alejandro Ceciliano, None; Adriana Fandiño, None; Claudia Sampor, None; Guillermo Chantada, None; Paula Schaiquevich, None
  • Footnotes
    Support  CONICET PIP# 11220090100343
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1881. doi:
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      Paula J. Taich, Emiliano Buitrago, Andres Porta, Alejandro Ceciliano, Adriana Fandiño, Claudia Sampor, Guillermo Chantada, Paula Schaiquevich; Clinical Pharmacokinetics Of Melphalan After Super-Selective Ophthalmic Artery Infusion In Children With Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1881.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To characterize melphalan plasma pharmacokinetics (PK) after super-selective ophthalmic artery infusion (SSOAI) in pediatric patients with retinoblastoma. To study possible relationships between dose and systemic exposure with ocular and hematological toxicity.

Methods: : Refractory/relapsed children with retinoblastoma were cannulated one or both (tandem therapy) ophthalmic arteries and between 3 to 6 mg of melphalan were infused under general anesthesia. Serial blood samples were collected and assayed for melphalan by HPLC. Population pharmacokinetic analysis was performed with Monolix 3.2 and associations between covariates (age, weight and body surface area) and pharmacokinetic parameters were evaluated. Relationships between systemic exposure (AUC) and dosage (dose/kg) with toxicity were evaluated.

Results: : A total of 30 administrations to one eye and 6 bilateral tandem administrations from 17 patients were evaluated. A two-compartment model was selected. A large inter-individual variability (IIV) in clearance (CLc) and volume of distribution of the central compartment (Vc) was observed accounting for 57 % and 58 % for CLc and Vc, respectively. Total body weight explained 81 % and 15 % of the IIV in CLc and Vc, respectively. The final median PK parameters included CLc: 0.50 L/h*kg and Vc: 0.12 L/kg. AUC was significantly higher in patients that received dosages greater than 0.48 mg/kg of melphalan (p< 0.05) and 50 % of these AUCs corresponded to patients that showed hematological toxicities grade 3/4 and were under tandem therapy. The ophtalmological toxicity was mild.

Conclusions: : This is the first report of melphalan pharmacokinetics after SSOI in retinoblastoma patients. Systemic exposure was statistically related to dosage (mg/kg) with 50 % probability of hematological toxicity in tandem therapy patients. This results support future studies of dose escalation in this patient population.

Keywords: retinoblastoma • vitreous 
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