Blood levels of ruthenium following repeated treatments with the antimetastatic compound NAMI-A in healthy beagle dogs.
NAMI-A is a new generation ruthenium compound which is entering phase-I clinical trials anti-metastatic agent. This study analyses the effects of the i.v. injection of NAMI-A to healthy Beagle dogs at increasing doses from 0.4 (low) 4 (mid) and 8 (high) mg/kg/day, given for 5 consecutive days. Only mild signs of toxicity, consisting of emesis and mucoid faeces, from which animals completely recovered, occurred during treatment at the high dose. Decay of ruthenium concentration from the whole blood, 24 hr after 5-days treatment, was lower than that observed after 1-day treatment. T1/2 was about 20-23 hr, or slightly longer when the animals were hydrated with tap water prior to treatment; Cltot was 21-22 ml*hr-1, decreasing to 13 ml*hr-1 after hydration and increasing to 34 ml*hr-1 with the high dose. AUC was proportional to the dose used. Thus NAMI-A is well tolerated by healthy dogs with blood levels comparable to those obtained in mice treated with an about 10-times higher daily dose.
Sava
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Callerio Foundation, Institutes of Biological Research, via A. Fleming 22, Trieste, Italy. gsava@fc.univ.trieste.it
Cocchietto
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D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D012428:Ruthenium / Q000097:blood*; D017975:Ruthenium Compounds; D013045:Species Specificity; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D012428:Ruthenium; D004121:Dimethyl Sulfoxide