Pharmacokinetics of Adriamycin and cisplatin for anhepatic chemotherapy during liver transplantation

Yonson Ku, Nobuya Kusunoki, Tetsushi Kitagawa, Ichiro Maeda, Takumi Fukumoto, Takeshi Iwasaki, Masahiro Tominaga, Yasuyuki Suzuki, Yoshikazu Kuroda, Yusuke Tanigawara, Yoichi Saitoh

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We investigated the pharmacokinetics of cytotoxic anticancer agents administered under anhepatic conditions. Beagle dogs underwent either a sham operation consisting of laparotomy only (control group, n = 11) or a laparotomy and total hepatectomy under venovenous bypass (anhepatic group, n 12). Each dog received a bolus intravenous injection of either Adriamycin (1 mg/kg) or cisplatin (1 mg/kg). The plasma and urine concentrations of each drug were measured at intervals for up to 2 h after drug injection. The dogs given Adriamycin were then sacrificed to determine tissue drug concentrations in the liver (controls only), spleen, kidney, heart, lung, skeletal muscle and small intestine. The control and anhepatic groups showed similar Adriamycin profiles during the initial 5 min after drug injection. However, subsequently, the plasma Adriamycin concentrations remained persistently higher in the anhepatic dogs than in the controls, yielding a two-fold elevation of the mean area under the concentration-time curve in the anhepatic group (P<0.01 vs controls). The renal clearance values did not significantly differ between the two groups. The tissue Adriamycin concentrations in all measured organs, excluding the liver, were higher in the anhepatic group than in the controls. In a second set of experiments with cisplatin, the plasma platinum concentrations did not significantly differ between the two groups throughout the time course. However, the renal clearance of platinum in the anhepatic dogs showed a fourfold increase compared with that in the controls (P<0.01). These pharmacokinetics data suggest that Adriamycin carries the risk of increased systemic toxicities, while cisplatin may be associated with increased renal toxicity when administered during the anhepatic period of liver transplantation.

Original languageEnglish
Pages (from-to)457-462
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume40
Issue number6
DOIs
Publication statusPublished - 1997 Sep 25
Externally publishedYes

Keywords

  • Adriamycin
  • Anhepatic chemotherapy
  • Cisplatin
  • Hepatocellular carcinoma
  • Liver transplantation

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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