Evaluation of safety parameters and changes in serum concentration in liver transplant recipients treated with doxorubicin during the anhepatic period

Shogo Kobayashi, Hiroshi Wada, Naoki Hama, Hirofumi Akita, Koichi Kawamoto, Hidetoshi Eguchi, Koji Umeshita, Yuichiro Doki, Masaki Mori, Hiroaki Nagano

研究成果: Contribution to journalArticle査読

1 被引用数 (Scopus)

抄録

Purpose: Because of the recurrence of hepatocellular carcinoma (HCC) at the graft after liver transplantation, circulating HCC cells may be present during the anhepatic period. Intravenous doxorubicin (DOX) is used during the anhepatic period to combat these cells; however, pharmacokinetics data have been poorly analyzed. This study aims to investigate DOX administration during the anhepatic period. Patients and methods: We administered 5 mg/m2 DOX immediately after liver removal and compared serum DOX concentrations at several intervals during the anhepatic period in patients who underwent liver transplantation because of liver cirrhosis and HCC (n = 3) and patients who underwent liver resection owing to HCC with portal vein tumor thrombi (n = 5). We also measured serum DOX concentrations and pharmacokinetic parameters in transplant patients that received 3-15 mg/m2 DOX (n = 3 per dose level). We evaluated transplant patients' adverse drug reactions and survival. Results: At 10 and 30 min after DOX administration, serum DOX concentrations were elevated two- to threefold in transplant patients versus resection patients. Dose escalation in transplant patients exhibited a prolonged T 1/2 in the one-compartment model and T 1/2 β in the two-compartment model, as well as a dose-dependent elevation of the area under the curve. No obvious adverse drug reactions were noted at 3-15 mg/m2 DOX. In transplant patients, 5-year recurrence-free survival was 68.8 %; overall survival was 100.0 %. Conclusion: During the anhepatic period, serum DOX concentrations were elevated two- to threefold, T 1/2 was prolonged dose dependently, and up to 15 mg/m2 DOX could be safely administered.

本文言語英語
ページ(範囲)1325-1333
ページ数9
ジャーナルCancer chemotherapy and pharmacology
72
6
DOI
出版ステータス出版済み - 12 1 2013

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 毒物学
  • 薬理学
  • 癌研究
  • 薬理学(医学)

フィンガープリント

「Evaluation of safety parameters and changes in serum concentration in liver transplant recipients treated with doxorubicin during the anhepatic period」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル