[Evaluation of concomitant use of cyclosporin and percutaneous isolated liver perfusion under complete venous isolation and charcoal hemoperfusion].
It is difficult to administer an effective dose of cyclosporin A (CsA), a potent inhibitor of P-glycoprotein, to prevent multiple drug resistance due to its side effect. We herein evaluated the efficacy of concomitant use of this agent and complete hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). Dogs were divided into two groups; group I (n = 4), intraarterial infusion of only adriamycin (ADM) and group II (n = 4), intraarterial infusion of CsA and ADM. In both groups, ADM was intraarterially administered for 10 minutes under HVI.CHP. In addition, in group II, CsA infusion (0.3 mg/min.kg) was initiated 20 min prior to the start of ADM infusion and maintained for 30 min. The AUC (micrograms.min/ml) of ADM were 21.2 +/- 8.6 (mean +/- SD) and 28.4 +/- 10.3 in groups I and II, respectively, at prefilter (hepatic venous level) and 8.1 +/- 4.6 and 4.8 +/- 3.8, respectively, at postfilter, showing an effective drug elimination in both groups. The Cmax (micrograms/ml) were 14.1 +/- 2.2 at prefilter, 2.4 +/- 0.5 at postfilter, and 3.4 +/- 1.2 in systemic level. These results indicated that HVI.CHP allowed the high-dose CsA infusion required for P-gp inhibition in the liver and could reduce extraregional CsA leakage.
Kusunoki
N
N
First Dept. of Surgery, Kobe University School of Medicine.
Ku
Y
Y
Tanigawara
Y
Y
Maeda
I
I
Sugimoto
T
T
Muramatsu
S
S
Iwasaki
T
T
Tominaga
M
M
Kuroda
Y
Y
Saitoh
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002606:Charcoal / Q000627:therapeutic use; D010478:Chemotherapy, Cancer, Regional Perfusion; D016572:Cyclosporine / Q000008:administration & dosage*; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D006464:Hemoperfusion; D006503:Hepatic Veins; D008099:Liver / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D002606:Charcoal; D004317:Doxorubicin; D016572:Cyclosporine