title: Pharmacokinetic analysis of topotecan after superselective ophthalmic artery infusion and periocular administration in a porcine model.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Superselective OAI resulted in significantly higher vitreous concentrations and exposure and a trend toward lower systemic exposure than POI.
authors: Clinical Pharmacokinetics Unit, CONICET-Hospital de Pediatría JP Garrahan, Buenos Aires, Argentina.
authors: Paula
authors: P
authors: Schaiquevich
authors: Emiliano
authors: E
authors: Buitrago
authors: Alejandro
authors: A
authors: Ceciliano
authors: Adriana C
authors: AC
authors: Fandino
authors: Marcelo
authors: M
authors: Asprea
authors: Sergio
authors: S
authors: Sierre
authors: David H
authors: DH
authors: Abramson
authors: Guillermo F
authors: GF
authors: Bramuglia
authors: Guillermo L
authors: GL
authors: Chantada
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002404:Catheterization; D002851:Chromatography, High Pressure Liquid; D007261:Infusions, Intra-Arterial; D056965:Injections, Intraocular; D009880:Ophthalmic Artery / Q000378:metabolism*; D034421:Sus scrofa; D059004:Topoisomerase I Inhibitors / Q000493:pharmacokinetics*; D019772:Topotecan / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D059004:Topoisomerase I Inhibitors; D019772:Topotecan