Cisplatin pharmacokinetics in nontumoral pig liver treated with intravenous or transarterial hepatic chemoembolization.

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.