title: Irinotecan loaded in eluting beads: preclinical assessment in a rabbit VX2 liver tumor model.
abstract: OBJECTIVE
  The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform.
  
  
  METHODS
  Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver.
  
  
  RESULTS
  Twelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03).
  
  
  CONCLUSIONS
  Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.
authors.affiliation: Department of Interventional Radiology, Institute Gustave Roussy, Villejuif, 94805, France.
authors.forename: Pramod P
authors.initials: PP
authors.lastname: Rao
authors.forename: Florentina
authors.initials: F
authors.lastname: Pascale
authors.forename: Atman
authors.initials: A
authors.lastname: Seck
authors.forename: Anne
authors.initials: A
authors.lastname: Auperin
authors.forename: Laurence
authors.initials: L
authors.lastname: Drouard-Troalen
authors.forename: Frederic
authors.initials: F
authors.lastname: Deschamps
authors.forename: Christophe
authors.initials: C
authors.lastname: Teriitheau
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.forename: Alban
authors.initials: A
authors.lastname: Denys
authors.forename: Pierre
authors.initials: P
authors.lastname: Bize
authors.forename: Thierry
authors.initials: T
authors.lastname: de Baere
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016461:Chemoembolization, Therapeutic; D016503:Drug Delivery Systems; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D011817:Rabbits; D018709:Statistics, Nonparametric
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin; D002166:Camptothecin