Lattice intrahepatic doxorubicin with and without in-flow occlusion: a pharmacokinetic study of direct liver injection

• Published in: European journal of surgical oncology 2000-02, Vol.26 (1), p.73-79
• Main Authors: Averbach, A, Stuart, O.A, Chang, D, Sugarbaker, P.H
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - blood; Antibiotics, Antineoplastic - pharmacokinetics; Antibiotics, Antineoplastic - therapeutic use; Area Under Curve; Biological and medical sciences; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - secondary; Chromatography, High Pressure Liquid; colorectal liver metastases, doxorubicin, hepatoma, in-flow occlusion, intrahepatic chemotherapy, pharmacokinetics; Colorectal Neoplasms - pathology; Dogs; Doxorubicin - blood; Doxorubicin - pharmacokinetics; Doxorubicin - therapeutic use; Female; Gastroenterology. Liver. Pancreas. Abdomen; General pharmacology; Infusions, Intra-Arterial; Infusions, Intravenous; Injections, Intralesional - methods; Liver Neoplasms - blood; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Liver Neoplasms - secondary; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Random Allocation; Time Factors; Tumors
• ISSN: 0748-7983; 1532-2157
• DOI: 10.1053/ejso.1999.0744

Aim To assess possible improvements in drug delivery to unresectable liver tumours we investigated the pharmacokinetics of intrahepatic doxorubicin in the dog liver with and without inflow occlusion. Methods Using a lattice template, doxorubicin was injected into 16 sites (over a 9 cm2area) in each of three lobes of the liver for a total of 48 sites. The total doses of doxorubicin used were 4.8 mg and 96 mg (0.1 and 2 mg/site). Dogs with intravenous and intra-arterial delivery of the same total doses of doxorubicin were used as controls. Experiments using intrahepatic injection were performed with and without a 30 min occlusion of the hepatic artery, common bile duct and portal vein (inflow occlusion). The studies with vascular stasis were performed to determine if drug clearance from the injection sites and their plasma levels were reduced. Also, it was observed that blood and drug loss along the needle tract was reduced when inflow occlusion was used. Plasma and liver samples were harvested over a 90-min period and analysed by high pressure liquid chromatography (HPLC). Results In plasma mean peak levels and mean area under the curve (AUC) were significantly lower with intrahepatic doxorubicin (P