Mitomycin C toxicity and pharmacokinetics in mice given sulfur nucleophiles.
The sulfur nucleophiles, sodium thiosulfate (Na2S2O3) and N-acetylcysteine (NAC) given in maximally tolerated doses did not reduce the hematologic toxicity of high dose mitomycin C (MMC) in normal mice. In addition, neither sulfur nucleophile significantly altered the antileukemic activity of MMC. Pharmacokinetic studies of MMC in normal mice, demonstrated rapid plasma elimination (T1/2 beta = 0.53 hrs) and substantial drug distribution to the bone marrow which was enhanced by NAC. These results demonstrate a lack of MMC antidotal activity for Na2S2O3 and NAC.
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016685:Mitomycin; D008937:Mitomycins / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D013885:Thiosulfates / Q000494:pharmacology*
D000931:Antidotes; D008937:Mitomycins; D013885:Thiosulfates; D016685:Mitomycin; C017717:sodium thiosulfate; D000111:Acetylcysteine