Pharmacokinetic analysis of melphalan after superselective ophthalmic artery infusion in preclinical models and retinoblastoma patients.

SCHAIQUEVICH P, BUITRAGO E, TAICH P, TORBIDONI A, CECILIANO A, FANDINO A, ASPREA M, REQUEJO F, ABRAMSON DH, BRAMUGLIA GF, CHANTADA GL.

Invest Ophthalmol Vis Sci

IOVS

Año: 2012 vol. 53 p. 4205 - 4212

1552-5783

PURPOSE: To characterize melphalan pharmacokinetics after superselective ophthalmic artery infusion (SSOAI) in animals and children with retinoblastoma. METHODS: Vitreous and plasma samples of five Landrace pigs were obtained over a 4-hour period after SSOAI of melphalan (7 mg). Melphalan cytotoxicity was evaluated in retinoblastoma cell lines with and without topotecan. Plasma samples were obtained from 17 retinoblastoma patients after SSOAI of 3 to 6 mg of melphalan to one (n=14) or two eyes (n=3). Correlation between plasma pharmacokinetics and age, dosage, and systemic toxicity was studied in patients. RESULTS: In animals, melphalan peak vitreous levels were greater than its IC50 and resulted in 3-fold vitreous-to-plasma exposure. In patients, a large variability in pharmacokinetic parameters was observed and it was explained mainly by body weight (P