Pharmacokinetic advantage of intra-arterial hepatic oxaliplatin administration: comparative results with cisplatin using a rabbit VX2 tumor model.
The aim of this study was to compare intra-arterial hepatic administration (IAH) versus i.v. administration of oxaliplatin and cisplatin in a VX2 tumor model in rabbits. VX2 tumors were implanted in the livers of White New Zealand female rabbits and 2 weeks later they received either cisplatin (4 mg/kg) or oxaliplatin (6 mg/kg) administered by IAH or i.v. Platinum pharmacokinetic parameters were measured by atomic absorption spectrometry at baseline, 2, 5 10, 20, 40 and 60 min, and then at 2, 4, 6 and 24 h after drug administration. Animals were sacrificed 24 h after drug administration to measure platinum concentrations in various tissues. After IAH oxaliplatin administration, we observed a significant decrease for total and filterable platinum in the Cmax compared with i.v. administration (12.4 versus 18.2 microg/l; p=0.02 and 11.2 versus 17.3 microg/l; p=0.02, respectively). Significant differences in various tissue concentrations were reported when comparing IAH and i.v. administration of oxaliplatin with IAH administration offering an advantage over i.v. administration. No differences in pharmacokinetic parameters or platinum tissue accumulation were apparent between the IAH and i.v. administration with cisplatin. We conclude that there is a significant pharmacokinetic advantage to using oxaliplatin for locoregional IAH chemotherapy compared with i.v. administration.
Dzodic
Radan
R
Pharmacology Unit, Châtenay-Malabry, France; Institut Pasteur, Paris, France.
Gomez-Abuin
Gonzalo
G
Rougier
Philippe
P
Bonnay
Marc
M
Ardouin
Patrice
P
Gouyette
Alain
A
Rixe
Olivier
O
Ducreux
Michel
M
Munck
Jean-Nicolas
JN
D000818:Animals; D019540:Area Under Curve; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006499:Hepatic Artery; D007269:Injections, Intra-Arterial; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077150:Oxaliplatin; D010984:Platinum / Q000097:blood / Q000493:pharmacokinetics; D011817:Rabbits; D013997:Time Factors; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum; D002945:Cisplatin