J Pharm Pharmacogn Res 2(Suppl. 1): S17, 2014
Special supplement with the abstract book of LATINFARMA 2013
CO 032: SUPER-SELECTIVE OPHTHALMIC ARTERY CATHETERIZATION IN THE PIG AS A TRAINING MODEL WITH POSSIBLE IMPLICATIONS FOR RETINOBLASTOMA TREATMENT
Asprea M, Schaiquevich P, Requejo F, Buitrago E, Chantada G.
Introduction: Super-selective ophthalmic artery infusion was studied in a porcine model and compared to periocular administration as an alternative route for administration in retinoblastoma. Ophthalmic artery infusion of topotecan results in significantly higher vitreous exposure compared to periocular administration. Systemic exposure was low after both routes of administration, confirming feasibility of the method.
Aim: To develop a technique for local drug administration in a porcine model with potential translation to retinoblastoma chemotherapy treatment.
Material and methods: Six domestic Landrace pigs were included. In four, the ophthalmic artery catheterization was performed in an anesthesized animal under anticoagulation. A 5-French arterial sheath was placed in the femoral artery and a 5-F catheter was guided into the common carotid artery to the maxillary artery. The ophthalmic artery was super-selectively catheterized (OAI) using a microcatheter. Serial angiograms were performed. Super-selective OAI of topotecan (1 mg) toone eye and periocular injection (1 mg) to the fellow eye was performed after a wash-out period. Chemotherapy (topotecan) was delivered in a pulsating fashion. The microcatheter was removed and systematic procurement of vitreous and plasma samples was started immediately. Two other animals were only administered intraarterially (IA) with the same dose of chemotherapy through the external carotid, and plasma and vitreous samples were obtained. All animals were sacrificed at the end of the experiment according to an approved method of euthanasia.
Results: The ophthalmic artery of all six animals was successfully catheterized by means of the super-selective ophthalmic artery technique. Maximum total topotecan concentration in the vitreous (median, range) after OAI and IA was 131.8 ng/mL (112.9-138.7) and 5.4 ng/mL (4.7-6.1), respectively. Systemic exposure for topotecan was low after both modalities of administration with a median (range) value of 10.6 ng/h/mL (6.8-13.4).
Conclusion: We were able to develop the super-selective ophthalmic artery catheterization in a porcine model. Topotecan was infused using this technique and vitreous drug levels were 24 times higher than those attained after IA infusion of the same dose of chemotherapy. Topotecan systemic exposure was low and comparable between drug administration techniques. These results show the selectivity of the infusion to attain the ocular structures with potential implications in retinoblastoma treatment.