Marcelo Asprea

To characterize the vitreous and plasma pharmacokinetics of topotecan after ophthalmic artery infusion (OAI) subsequent to superselective artery catheterization and to compare it with periocular injection (POI). The ophthalmic artery of 4 pigs was catheterized and 1 mg of topotecan infused over a period of 30 minutes. The contralateral eye was subsequently used for administering topotecan by POI. Serial vitreous specimens were obtained by microdialysis and plasma samples collected and assayed for total and lactone topotecan. Maximum total topotecan concentration in the vitreous (median, range) was significantly higher after OAI compared with POI (131.8 ng/mL [112.9-138.7] vs. 13.6 ng/mL [5.5-15.3], respectively; P < 0.005). Median vitreous exposure calculated as area under the curve for total topotecan attained after OAI was significantly higher than after POI (299.8 ng·hour/mL [247.6-347.2] and 48.9 ng·hour/mL [11.8-63.4], respectively; P < 0.05). The vitreous to plasma exposure ratio was 29 after OAI and 3.4 after POI. Systemic exposure for total topotecan was low after both modalities of administration, with a trend to be lower after OAI compared with POI (10.6 ng·hour/mL [6.8-13.4] vs. 18.7 ng·hour/mL [6.3-21.7]; P = 0.54). Superselective OAI resulted in significantly higher vitreous concentrations and exposure and a trend toward lower systemic exposure than POI.

To describe a technique for micro catheterization of the external ophthalmic artery (EO) in pigs for investigational and training purposes. Carotid angiography was performed in seven male domestic pigs. The external ophthalmic artery was reached with a microcatheter in order to administer a neoplastic drug in the eye. The external ophthalmic artery could be found arising from the infraorbital (IO) artery in the bend of the internal maxillary (IM) artery. It could be reached in every animal. Following anatomic landmarks of the external carotid (EC) artery the ophthalmic artery can be easily reached and catheterized for training and investigational purposes.

To characterize melphalan pharmacokinetics after superselective ophthalmic artery infusion (SSOAI) in animals and children with retinoblastoma. 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. 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<0.05). A significantly higher systemic area under the curve was obtained in children receiving more than 0.48 mg/kg for bilateral tandem infusions (P<0.05). These children had 50% probability of grades 3-4 neutropenia. Plasma concentrations after 2 and 4 hours of SSOAI were significantly higher in these children (P<0.05). A synergistic cytotoxic effect of melphalan and topotecan was evident in cell lines. Potentially active levels of melphalan after SSOAI were achieved in the vitreous of animals. Low systemic exposure was found in animals and children. Doses greater than 0.48 mg/kg, given for bilateral tandem infusions, were associated with significantly higher plasma levels and increased risk of neutropenia. Synergistic in vitro cytotoxicity between melphalan and topotecan favors combination treatment.

Objective. 1. The creation of an aneurysm model in an arterial bifurcation for microsurgical training in rats. 2. To verify angiographically the aneurysms patency performing endovascular maneuvers. Material and method. 10 Wistar rats weighted 400-600g were ...

La creación de aneurismas experimentales en animales se ha convertido en estos últimos años en una actividad muy importante para la experimentación de elementos endovasculares oclusivos 1 . La comprobación de la permeabilidad y forma del aneurisma creado mediante la ...