title: Fate of the antimetastatic ruthenium complex ImH [trans-RuCl4(DMSO)Im] after acute i.v. treatment in mice.
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.
authors.affiliation: Callerio Foundation, Institute of Biological Research, Trieste, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cocchietto
authors.forename: G
authors.initials: G
authors.lastname: Salerno
authors.forename: E
authors.initials: E
authors.lastname: Alessio
authors.forename: G
authors.initials: G
authors.lastname: Mestroni
authors.forename: G
authors.initials: G
authors.lastname: Sava
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D019540:Area Under Curve; D001825:Body Fluid Compartments; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced; D051379:Mice; D008808:Mice, Inbred CBA; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D017975:Ruthenium Compounds; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D004121:Dimethyl Sulfoxide