Fate of the antimetastatic ruthenium complex ImH [trans-RuCl4(DMSO)Im] after acute i.v. treatment in mice

Anticancer Res. 2000 Jan-Feb;20(1A):197-202.

Abstract

The content of ruthenium in blood and different organs of healthy CBA mice was determined by AAS after single i.v. treatment of 200 mg kg-1 of NAMI-A, a new antimetastatic ruthenium compound. Ruthenium concentration in blood falls 5 min after i.v. treatment. In the kidney, ruthenium concentration is markedly higher than in any other analysed tissue. No ruthenium was detected in brains. Pharmacokinetic parameters for a mono- or a bi-compartment model are identifiable: t1/2 is 10.45 h vs 12.02 (t1/2 alpha 0.023 h + t1/2 beta 12 h) with Cltot of 1.60 ml*h-1 vs 1.59); Vd is 24.15 vs 27.48 ml and (model dependent) AUC is 689 vs 694 mg*L-1*h. AUC(0-->infinity) calculated by noncompartmental method (linear trapezoidal rule) is 719.77 mg*L-1*h. NAMI-A is rapidly cleared from the blood compartment immediately after i.v. administration. Apparently, there is no differential accumulation of ruthenium in the lungs which might account for a selective antimetastatic effect caused by a cytotoxic concentration in this site, nor in any other specific organ examined.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / toxicity
  • Area Under Curve
  • Body Fluid Compartments
  • Dimethyl Sulfoxide / administration & dosage
  • Dimethyl Sulfoxide / analogs & derivatives*
  • Dimethyl Sulfoxide / blood
  • Dimethyl Sulfoxide / pharmacokinetics
  • Dimethyl Sulfoxide / toxicity
  • Injections, Intravenous
  • Kidney Diseases / chemically induced
  • Mice
  • Mice, Inbred CBA
  • Models, Biological
  • Neoplasm Metastasis / prevention & control*
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / blood
  • Organometallic Compounds / pharmacokinetics*
  • Organometallic Compounds / toxicity
  • Ruthenium Compounds
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Ruthenium Compounds
  • imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III)
  • Dimethyl Sulfoxide