Transarterial embolization with sorafenib in animal livers: a pharmacokinetics study

J Vasc Interv Radiol. 2013 Nov;24(11):1657-63.e1. doi: 10.1016/j.jvir.2013.08.007. Epub 2013 Sep 21.

Abstract

Purpose: To assess the safety and feasibility of the targeted delivery of the antiangiogenic drug sorafenib to the liver using transarterial chemoembolization methodology as a novel approach to hepatocellular carcinoma (HCC) therapy.

Materials and methods: Seven healthy New Zealand white rabbits were used in the study. After placement of a catheter in the common hepatic artery, six rabbits were treated with chemoembolization of sorafenib in iodized oil (Lipiodol) (sorafenib dose 0.1 mg/kg), and one rabbit received Lipiodol only. Liquid chromatography tandem mass spectrometry was used to measure the concentration of sorafenib in the peripheral blood and liver tissue 24 hours and 72 hours after treatment. Histochemical staining of the liver sections and biochemical measurements were performed.

Results: The administration of sorafenib in Lipiodol emulsions by transarterial chemoembolization resulted in sorafenib concentrations of 794 ng/g ± 240 and 64 ng/g ± 15 in the liver tissue 24 hours and 72 hours after treatment. The average liver-to-serum ratios 24 hours and 72 hours after treatment were approximately 14 and 22. The histochemical staining of the liver tissue sections and aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase and total bilirubin concentrations indicated no significant liver damage.

Conclusions: Transarterial chemoembolization with sorafenib in Lipiodol is an effective methodology for the localized delivery of this drug to the liver and has possible practical implications in therapeutic interventions for the treatment of hepatocellular carcinoma.

Keywords: ALT; AST; AcCN; GGT; HCC; LC-ESI-MS/MS; LC-MS/MS; acetonitrile; alanine aminotransferase; aspartate aminotransferase; hepatocellular carcinoma; liquid chromatography electrospray ionization mass spectrometry; liquid chromatography tandem mass spectrometry; γ-glutamyltransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / metabolism
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / blood
  • Angiogenesis Inhibitors / pharmacokinetics*
  • Animals
  • Bilirubin / metabolism
  • Chemoembolization, Therapeutic / methods*
  • Chromatography, High Pressure Liquid
  • Ethiodized Oil / administration & dosage
  • Feasibility Studies
  • Hepatic Artery*
  • Liver / blood supply*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Models, Animal
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Niacinamide / blood
  • Niacinamide / pharmacokinetics
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / blood
  • Phenylurea Compounds / pharmacokinetics*
  • Rabbits
  • Sorafenib
  • Tandem Mass Spectrometry
  • gamma-Glutamyltransferase / metabolism

Substances

  • Angiogenesis Inhibitors
  • Phenylurea Compounds
  • Niacinamide
  • Ethiodized Oil
  • Sorafenib
  • gamma-Glutamyltransferase
  • Alanine Transaminase
  • Bilirubin