Evaluation of concomitant use of cyclosporin and percutaneous isolated liver perfusion under complete venous isolation and charcoal hemoperfusion

N. Kusunoki, Y. Ku, Yusuke Tanigawara, I. Maeda, T. Sugimoto, S. Muramatsu, T. Iwasaki, M. Tominaga, Y. Kuroda, Y. Saitoh

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 (μg · 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 C(max) (μg/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.

Original languageEnglish
Pages (from-to)1408-1411
Number of pages4
JournalJapanese Journal of Cancer and Chemotherapy
Volume23
Issue number11
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Hemoperfusion
Charcoal
Doxorubicin
Cyclosporine
Perfusion
Liver
Intra Arterial Infusions
Multiple Drug Resistance
P-Glycoprotein
Area Under Curve
Dogs
Pharmaceutical Preparations

Keywords

  • Charcoal hemoperfusion
  • Cyclosporin A
  • High dose chemotherapy
  • P glycoprotein

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

Cite this

Evaluation of concomitant use of cyclosporin and percutaneous isolated liver perfusion under complete venous isolation and charcoal hemoperfusion. / Kusunoki, N.; Ku, Y.; Tanigawara, Yusuke; Maeda, I.; Sugimoto, T.; Muramatsu, S.; Iwasaki, T.; Tominaga, M.; Kuroda, Y.; Saitoh, Y.

In: Japanese Journal of Cancer and Chemotherapy, Vol. 23, No. 11, 1996, p. 1408-1411.

Research output: Contribution to journalArticle

Kusunoki, N, Ku, Y, Tanigawara, Y, Maeda, I, Sugimoto, T, Muramatsu, S, Iwasaki, T, Tominaga, M, Kuroda, Y & Saitoh, Y 1996, 'Evaluation of concomitant use of cyclosporin and percutaneous isolated liver perfusion under complete venous isolation and charcoal hemoperfusion', Japanese Journal of Cancer and Chemotherapy, vol. 23, no. 11, pp. 1408-1411.
Kusunoki, N. ; Ku, Y. ; Tanigawara, Yusuke ; Maeda, I. ; Sugimoto, T. ; Muramatsu, S. ; Iwasaki, T. ; Tominaga, M. ; Kuroda, Y. ; Saitoh, Y. / Evaluation of concomitant use of cyclosporin and percutaneous isolated liver perfusion under complete venous isolation and charcoal hemoperfusion. In: Japanese Journal of Cancer and Chemotherapy. 1996 ; Vol. 23, No. 11. pp. 1408-1411.
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AU - Kusunoki, N.

AU - Ku, Y.

AU - Tanigawara, Yusuke

AU - Maeda, I.

AU - Sugimoto, T.

AU - Muramatsu, S.

AU - Iwasaki, T.

AU - Tominaga, M.

AU - Kuroda, Y.

AU - Saitoh, Y.

PY - 1996

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N2 - 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 (μg · 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 C(max) (μg/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.

AB - 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 (μg · 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 C(max) (μg/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.

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