[Pharmacokinetic comparison of intraarterial and intraportal infusion of adriamycin in regional chemotherapy of the liver].
We investigated the adriamycin (ADR) pharmacokinetics following intraarterial and intraportal infusion under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). HVI.CHP was used to measure the first-pass amount of adriamycin through the liver and to reduce hepatic re-entry of the drug. Beagles underwent a 10-min ADR infusion (1 mg/kg) either through the hepatic artery (group I, n = 5) or the portal vein (group II, n = 5) under a 20-min HVI.CHP. During HVI.CHP, the hepatic venous flow rate and plasma ADR levels in prefilter (hepatic venous level), postfilter and peripheral blood were serially measured. Based on these measurements, the hepatic extraction ratio (HER) of ADR was calculated. Areas under the time-concentration curves of prefilter levels in groups I and II were 6.1 +/- 1.6 and 16.9 +/- 5.0 micrograms.min/ml, respectively, showing a significant difference between two groups (p < 0.01). On the contrary, HER of group I (81.2%) was significantly higher than that of group II (47.2%, p < 0.01). These results indicate that intraarterial infusion of ADR is superior to intraportal infusion in terms of local drug delivery to the liver and systemic drug toxicities.
Shiotani
M
M
First Dept. of Surgery, Kobe University School of Medicine.
Ku
Y
Y
Kusunoki
N
N
Kitagawa
T
T
Maeda
I
I
Tominaga
M
M
Tanigawara
Y
Y
Kuroda
Y
Y
Saitoh
Y
Y
D000818:Animals; D010478:Chemotherapy, Cancer, Regional Perfusion; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006464:Hemoperfusion; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000378:metabolism*; D011168:Portal System
D004317:Doxorubicin