Pharmacokinetics of a novel anticancer ruthenium complex (KP1019, FFC14A) in a phase I dose-escalation study

Anticancer Drugs. 2009 Feb;20(2):97-103. doi: 10.1097/CAD.0b013e328322fbc5.

Abstract

A phase I and pharmacokinetic study was carried out with the new ruthenium complex indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019, FFC14A). Seven patients with various types of solid tumours refractory to standard therapy were treated with escalating doses of KP1019 (25-600 mg) twice weekly for 3 weeks. No dose-limiting toxicity occurred. Ruthenium plasma concentration-time profiles after the first dose and under multiple-dose conditions were analysed using a compartmental approach. The pharmacokinetic disposition was characterised by a small volume of distribution, low clearance and long half-life. Only a small fraction of ruthenium was excreted renally. The area under the curve values increased proportionally with dose indicating linear pharmacokinetics.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Female
  • Humans
  • Indazoles / administration & dosage*
  • Indazoles / adverse effects
  • Indazoles / pharmacokinetics*
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Models, Biological
  • Neoplasms / drug therapy*
  • Organometallic Compounds
  • Ruthenium Compounds / administration & dosage*
  • Ruthenium Compounds / adverse effects
  • Ruthenium Compounds / pharmacokinetics*

Substances

  • Antineoplastic Agents
  • Indazoles
  • Organometallic Compounds
  • Ruthenium Compounds
  • indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))