[Pharmacokinetic evaluation of complete infrarenal inferior vena caval isolation and charcoal hemoperfusion for intra-arterial chemotherapy of pelvic tumors].
Regional chemotherapy for malignant pelvic tumors is disappointing due to the poor tumor response and dose-limiting systemic toxicity. This study was designed to determine whether a novel venous isolation-charcoal hemoperfusion system could limit systemic exposure to chemotherapeutic agents after regional arterial infusion. Adriamycin (2 mg/kg) was continuously administered in the internal iliac arteries of beagles under complete isolation of the infrarenal inferior vena cava and extracorporeal charcoal hemoperfusion (IVCI.CHP). Control beagles received adriamycin at the same dosage without IVCI.CHP. Plasma adriamycin concentrations were measured in the left carotid artery (systemic level) at intervals of up to 40 minutes after the start of drug infusion. In animals with IVCI.CHP, the drug levels were also determined at the inlet and outlet of a CHP filter. The mean drug extraction ratios by the CHP filter averaged 88%. As a result, animals with IVCI.CHP showed a significant reduction in systemic drug levels at all measuring time points compared to controls. The peak systemic levels of adriamycin were 0.8 +/- 0.1 and 2.3 +/- 0.8 micrograms/ml, respectively, in IVCI.CHP and control animals (p < 0.01). IVCI.CHP accomplished a significant reduction in systemic exposure to adriamycin after iliac arterial infusion. This novel system will allow regional delivery of high-dose cytotoxic agents with little systemic toxicity for pelvic tumors.
Maeda
I
I
First Dept. of Surgery, Kobe University School of Medicine.
Ku
Y
Y
Tominaga
M
M
Iwasaki
T
T
Kitagawa
T
T
Shiotani
M
M
Kuroda
Y
Y
Saitoh
Y
Y
D000818:Animals; D002606:Charcoal; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006464:Hemoperfusion; D007261:Infusions, Intra-Arterial; D010386:Pelvic Neoplasms / Q000378:metabolism / Q000628:therapy*; D014682:Vena Cava, Inferior
D002606:Charcoal; D004317:Doxorubicin