title: Cisplatin pharmacokinetics in nontumoral pig liver treated with intravenous or transarterial hepatic chemoembolization.
abstract: OBJECTIVE
  To evaluate cisplatin (CDDP) pharmacokinetics after its intravenous (IV) or intrahepatic arterial administration (IHA) in healthy pigs with or without embolization by absorbable gelatine.
  
  
  METHODS
  We analysed plasmatic and hepatic drug concentration in four groups of six mini-pigs each according to the modality of administration of CDDP (1 mg/kg): IV, IHA, IHA with partial embolization using absorbable gelatine (IHA-Pe), and IHA with complete embolization (IHA-Te). Unbounded plasmatic and hepatic platinum concentrations were measured. Concentration and pharmacokinetics parameters were compared using analysis of variance.
  
  
  RESULTS
  For all groups, there was a rapid and biexponential decrease in free platinum concentration. Plasmatic terminal half-life (T(1/2)) was significantly decreased after embolization at 191, 178, 42, and 41 min after IV, IHA, IHA-Pe, and IHA-Te administration, respectively. Maximal plasmatic concentration and systemic exposure to CDDP (AUC(24)) values were significantly decreased after embolization (C(max)                   p = 0.0075; AUC(24)                   p = 0.0053). Hepatic CDDP concentration rapidly peaked and then decreased progressively. After 24 h, the residual concentration represented 45, 47, 60, and 63 % of C(max), respectively, after IV, IHA, IHA-Pe, and IHA-Te. Hepatic T(1/2) and AUC(∞) values were increased after embolization, but the differences were not statistically significant.
  
  
  CONCLUSIONS
  This preliminary study confirms the feasibility of a pig model to study systemic and hepatic CDDP pharmacokinetics. Systemic exposure is lower after embolization, which could minimize systemic toxicity. Hepatic T(1/2) elimination and hepatic exposition values are increased with IHA compared with IV administration.
authors.affiliation: Pôle de Radiologie, CHU Clermont-Ferrand, 58 Rue Montalembert, 63000, Clermont-Ferrand, France. pchabrot@chu-clermontferrand.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Chabrot
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cardot
authors.forename: Pierre
authors.initials: P
authors.lastname: Guibert
authors.forename: François
authors.initials: F
authors.lastname: Bouculat
authors.forename: Lucie
authors.initials: L
authors.lastname: Cassagnes
authors.forename: Anne
authors.initials: A
authors.lastname: Léger-Enreille
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Buc
authors.forename: Pierre
authors.initials: P
authors.lastname: Dechelotte
authors.forename: Gilles
authors.initials: G
authors.lastname: Bommelaer
authors.forename: Louis
authors.initials: L
authors.lastname: Boyer
authors.forename: Armand
authors.initials: A
authors.lastname: Abergel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016461:Chemoembolization, Therapeutic; D002945:Cisplatin / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects*; D008297:Male; D011897:Random Allocation; D013552:Swine; D013556:Swine, Miniature
chemical_list: D002945:Cisplatin