Université d'Auvergne Clermont1 | CNRS

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Cisplatin Pharmacokinetics in Nontumoral Pig Liver Treated With Intravenous or Transarterial Hepatic Chemoembolization.

TitleCisplatin Pharmacokinetics in Nontumoral Pig Liver Treated With Intravenous or Transarterial Hepatic Chemoembolization.
Publication TypeJournal Article
Year of Publication2012
AuthorsChabrot, P., J. - M. Cardot, P. Guibert, F. Bouculat, L. Cassagnes, A. Léger-Enreille, E. Buc, P. Dechelotte, G. Bommelaer, L. Boyer, and A. Abergel
JournalCardiovascular and interventional radiology
Date Published2012 Apr 24
ISSN1432-086X
Abstract

PURPOSE: To evaluate cisplatin (CDDP) pharmacokinetics after its intravenous (IV) or intrahepatic arterial administration (IHA) in healthy pigs with or without embolization by absorbable gelatine. MATERIAL AND 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. CONCLUSION: 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.

DOI10.1007/s00270-012-0386-0
Alternate JournalCardiovasc Intervent Radiol