Alteration in the pharmacokinetics of hemoglobin-vesicles in a rat model of chronic liver cirrhosis is associated with kupffer cell phagocyte activity

Kazuaki Taguchi, Mayumi Miyasato, Hiroshi Watanabe, Hiromi Sakai, Eishun Tsuchida, Hirohisa Horinouchi, Koichi Kobayashi, Toru Maruyama, Masaki Otagiri

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The hemoglobin-vesicle (HbV) is a cellular, hemoglobin-based oxygen carrier. Our previous pharmacokinetic studies demonstrated that the liver is strongly associated with the metabolism and excretion of HbV. The aim of this study was to evaluate the pharmacokinetics of HbV in a chronic cirrhosis rat (CCR) model induced by carbon tetrachloride (CCl4) and explore whether liver functional parameters and Kupffer cell (KC) phagocyte activity are related to the pharmacokinetics of HbV. The CCRs were induced three times weekly by intraperitoneal administration of CCl4 for 8 weeks and categorized as Child-Pugh grade B. To analyze the pharmacokinetics, the CCRs were given a single intravenous injection of 3H-HbV (1400 mg of Hb/kg). The total clearance and hepatic distribution of HbV were negatively correlated with plasma aspartate aminotransferase (AST) levels (p = 0.007). In addition, the phagocyte index was negatively correlated with plasma AST levels (p = 0.047). The excretion of lipid components in feces was also negatively correlated with plasma AST levels (p = 0.049). In conclusion, alteration in the pharmacokinetics of HbV in CCRs can be attributed to a decrease in KC phagocyte activity and the extent of damage to parenchymal cells. This represents the first demonstration of the pharmacokinetics of a liposome preparation in chronic liverimpairment.

Original languageEnglish
Pages (from-to)775-783
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number2
DOIs
Publication statusPublished - 2011 Feb
Externally publishedYes

Keywords

  • Biliary excretion
  • Hepatocyte
  • Liposomes
  • Metabolism
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science

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