Pharmacokinetic analysis of topotecan after superselective ophthalmic artery infusion and periocular administration in a porcine model

P. SCHAIQUEVICH; BUITRAGO E; CECILIANO A; FANDINO A; ASPREA M; SIERRE S; ABRAMSON DH; BRAMUGLIA G; CHANTADA G

RETINA

LIPPINCOTT WILLIAMS & WILKINS

Año: 2012 vol. 32 p. 387 - 395

0275-004X

Purpose: To characterize the vitreous and plasma pharmacokinetics of topotecan after ophthalmic artery infusion (OAI) following super-selective artery catheterization and to compare it with periocular (POI) administration. Methods: The ophthalmic artery of 4 pigs was catheterized and 1 mg of topotecan was infused over 30 minutes. The contralateral eye was used for administering topotecan by POI. Serial vitreous specimens were obtained by microdialysis and plasma samples were collected and assayed for total and lactone topotecan. Results: Maximum total topotecan concentration in the vitreous (median, range) was significantly higher after OAI compared to POI (131.8 ng/ml (112.9-138.7) versus 13.6 ng/ml (5.5-15.3), respectively (p<0.005). Median vitreous exposure (AUCvit) to total topotecan attained after OAI was significantly higher than after POI (299.8 ng*h/ml (247.6- 347.2) and 48.9 ng*h/ml (11.8- 63.4), respectively) (p<0.05). The ratio between vitreous-to-plasma exposures was 29 and 3.4 after OAI and POI, respectively. Systemic exposure for total topotecan was low after for both modalities of administration with a trend to be lower after OAI compared to POI (10.6 ng*h/ml (6.8-13.4) versus 18.7 ng*h/ml (6.3-21.7); p = 0.54).     Conclusion: Super-selective ophthalmic artery infusion resulted in significantly higher vitreous and a trend towards to lower systemic exposure than periocular administration.