Hepatic artery infusion of doxorubicin with hepatic venous drug extraction.
Hepatic artery infusion (HAI) has been used to take advantage of the steep dose-response relationship characteristic of chemotherapeutic agents. Systemic toxicity, however, remains the dose limiting factor for HAI of low hepatic extraction drugs. This investigation compared the pharmacokinetics of doxorubicin administered using a system that combines HAI and hepatic venous drug extraction (HVDE) versus systemic administration without HVDE. HAI was accomplished by transfemoral cannulation of the hepatic artery. HVDE was aided by use of a double-balloon catheter inserted fluoroscopically via femoral vein cutdown into the inferior vena cava. Inflation of the balloons above and below the hepatic veins allowed collection of hepatic venous effluent. Hepatic venous blood was pumped through the double-balloon catheter into an extracorporeal circuit with activated carbon filters to extract drug prior to return to the systemic circulation. Domestic female swine (25-35 kg) received 3 mg/kg doxorubicin over 90 min via HAI. HVDE was performed for 240 min following initiation of HAI (Time 0-240 min). Control swine underwent hepatic venous isolation using the double-balloon catheter without drug filtration and received 3 mg/kg doxorubicin over 90 min via systemic vein (SYSI). Serum and myocardial doxorubicin and doxorubicinol levels were assayed using HPLC. Blood was serially sampled from hepatic vein blood, from the extracorporeal circuit after filtration, and from a systemic artery. Area under the curve (AUC) was integrated from time-concentration plots over Time 0-180 min.(ABSTRACT TRUNCATED AT 250 WORDS)
August
D A
DA
Division of Surgical Oncology, University of Michigan, Ann Arbor 48109-0331.
Verma
N
N
Andrews
J C
JC
Vaerten
M A
MA
Brenner
D E
DE
D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006439:Hemodynamics; D006499:Hepatic Artery; D006503:Hepatic Veins / Q000378:metabolism*; D007261:Infusions, Intra-Arterial; D009206:Myocardium / Q000378:metabolism; D009994:Osmolar Concentration; D013552:Swine
D004317:Doxorubicin; C010013:adriamycinol