Extracorporeal cisplatin removal using direct hemoperfusion under hepatic venous isolation for hepatic arterial chemotherapy: An experimental study on pharmacokinetics

Abstract

This study was undertaken to pharmacokinetically evaluate the efficacy of direct hemoperfusion under hepatic venous isolation (HVI-DHP) to cisplatin (CDDP) removal during hepatic arterial infusion. CDDP (2–4 mg/kg) was administered continuously to mongrel dogs through the hepatic artery for 10 min. Plasma levels and tissue concentrations were then compared between animals receiving CDDP alone (group 1, n=4) and those treated with additional HVI-DHP for 20 min (group 2, n=6). The peak CDDP levels in the right external jugular vein (systemic level) were 6.10±1.31 (mean±SD) and 1.41±0.12 μg/ml in groups 1 and 2 at a dosage of 2 mg/kg, respectively (P<0.01). The estimated drug removal rates in group 2 animals at dosages of 2 and 4 mg/kg were 45.7 (mean, n=5) and 46.9% (n=1), respectively. The tissue concentrations of CDDP of the liver 30 min after the initiation of infusions were similar in both groups. The values of the liver, the heart, and the kidney were 1.90±0.55, 0.50±0.16, and 3.90±2.50 μg/g of wet tissue weight, respectively, in group 1. In contrast, tissue levels of the heart and the kidney in group 2 animals were significantly reduced, with the values at a dosage of 2 mg/kg being 0.21±0.03 μg/g (P<0.01) and 0.86±0.53 μg/g (P<0.05), respectively. This study demonstrated that the extrahepatic distribution of CDDP during hepatic arterial infusion can be reduced significantly by the concomitant use of HVI-DHP.