Extracorporeal removal of anticancer drugs in hepatic artery infusion: the effect of direct hemoperfusion combined with venovenous bypass.
The effect of a new extracorporeal system combining direct hemoperfusion (DHP) with venovenous bypass was evaluated in the elimination of anticancer drugs in hepatic artery infusion. Adriamycin (3 mg/kg) and mitomycin C (1 mg/kg) were given to mongrel dogs through the hepatic artery with three different durations of 1, 10, and 20 minutes. Plasma drug levels were determined at the inlet and outlet of DHP and right external jugular vein (systemic level). Blood flow through DHP averaged 200 ml/min. In dogs without DHP (group I; n = 4), systemic levels of adriamycin and mitomycin C increased rapidly with 1-minute infusion, reaching the peak values of 6.61 +/- 2.44 (mean +/- SD) and 2.20 +/- 1.05 micrograms/ml, respectively. With DHP under single venous bypass (group II; n = 5), the peak values were reduced to 1.25 +/- 1.02 and 0.79 +/- 0.52 microgram/ml. Moreover, the peak levels were markedly reduced by DHP under hepatic venous isolation (group III; n = 6), the values being 0.41 +/- 0.15 and 0.13 +/- 0.07 microgram/ml with 1-minute infusion. The drug-removal rates were improved substantially in group III compared with group II. The longer the duration of infusion, the higher the removal rates tended to be in group III. These results indicate that effective elimination of anticancer drugs can be accomplished by this system during intraarterial chemotherapy of the liver.
Ku
Y
Y
First Department of Surgery, Kobe University School of Medicine, Japan.
Saitoh
M
M
Nishiyama
H
H
Fujiwara
S
S
Iwasaki
T
T
Tominaga
M
M
Maekawa
Y
Y
Ohyanagi
H
H
Saitoh
Y
Y
D000042:Absorption; D000818:Animals; D001794:Blood Pressure; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D005112:Extracorporeal Circulation; D006464:Hemoperfusion; D006499:Hepatic Artery / Q000378:metabolism*; D007261:Infusions, Intra-Arterial; D016685:Mitomycin; D008937:Mitomycins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D013997:Time Factors
D008937:Mitomycins; D016685:Mitomycin; D004317:Doxorubicin