INVESTIGADORES
SCHAIQUEVICH Paula Susana
congresos y reuniones científicas
Título:
Topotecan pharmacokinetics after superselective ophthalmic artery infusion and periocular administration in the pig.
Autor/es:
SCHAIQUEVICH P; BUITRAGO E; CECILIANO A; FANDIÑO A; ASPREA M; SIERRE S; ABRAMSON DH; BRAMUGLIA G; CHANTADA G
Lugar:
Fort Lauderdale
Reunión:
Congreso; Association for Research in Vision and Ophthalmology (ARVO), Annual Meeting; 2010
Resumen:
Purpose: To characterize and compare topotecan
pharmacokinetics in the vitreous and plasma of a porcine model after ophthalmic
artery infusion (OAI) following super-selective artery catheterization with
respect to periocular (POA) administration.Methods: The ophthalmic artery was catheterized and 1 mg of
topotecan was infused over 30 minutes. After a drug wash-out period, the
contralateral eye was used for administering the same dose of topotecan by POA.
Serial vitreous specimens were obtained by microdialysis and plasma samples
were collected and assayed for topotecan. Pharmacokinetic parameters were calculated
and compared between the two routes of topotecan administration.Results: Maximum vitreous total concentration (median, range) was
significantly higher after OAI (131.8, 112.9-138.7 ng/ml) compared to POA
(13.6, 5.5-15.3 ng/ml; p<0.005). The median total topotecan concentration in
the vitreous after four hours of OAI was 35.8 (16.9- 42.4) ng/ml compared to
4.2 (1.5- 5.7) ng/ml after POA. Total topotecan vitreous exposure (AUCvit)
after OAI was significantly higher than after POA (299.8, 247.6- 347.2 ng*h/ml
and 48.9, 11.8- 63.4 ng*h/ml, respectively; p<0.05). The ratio between
vitreous-to-plasma exposures was 29 and 3.4 after OAI and POA, respectively.
Systemic exposure for total topotecan was low after both routes of topotecan
administration with a trend to be lower after OAI compared to POA (p = 0.54).Conclusions: Potentially active levels against retinoblastoma
were attained over the whole studied period after OAI in the pig.
Super-selective ophthalmic artery infusion resulted in significantly higher
vitreous and a trend towards to lower systemic exposure than periocular
administration.