Influence of age on antileukemic action, subacute toxicity and tissue distribution of ambazone in B6D2F1 mice.
The influence of age of experimental animals on the antileukemic activity, toxicity and distribution of ambazone, a new potential antineoplastic agent, was studied in 2- and 12-month-old B6D2F1 mice. The predominant effect observed was a significant reduction of the antileukemic action of this compound in old-aged mice. Together with a slight increase in several toxicity parameters this caused a marked reduction of the therapeutic index in 12-month-old mice compared to younger individuals. Furthermore, a general tendency to increased ambazone levels in liver, kidneys and thymus of old-aged mice was observed. Our data therefore provide further evidence that age has to be taken into consideration as one factor that may account for the variety of drug response frequently observed during clinical therapy with anticancer agents.
Amlacher
R
R
Central Institute of Microbiology and Experimental Therapy, Academy of Sciences of the GDR, Jena.
Baumgart
J
J
Härtl
A
A
Weber
H
H
Kühnel
H J
HJ
Schulze
W
W
Hoffmann
H
H
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D007928:Lethal Dose 50; D007941:Leukemia P388 / Q000188:drug therapy* / Q000378:metabolism; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D009368:Neoplasm Transplantation; D014018:Tissue Distribution / Q000502:physiology
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; C037931:1,4-benzoquinone guanylhydrazone thiosemicarbazone; D008935:Mitoguazone