[Butoctamide enhancement of the antitumor activity of 6-mercaptopurine on Ehrlich solid tumors in mice (author's transl)].
Effects of butoctamide (N-(2-ethylhexyl)-3-hydroxybutyramide, L-2) on the antitumor activity of 6-mercaptopurine (6-MP) against Ehrlich solid tumors in mice were investigated. No change was observed in tumor growth after either oral or intraperitoneal administration of butoctamide (100 mg/kg/day X 7). This drug increased the activity of a  low dose of 6-MP (2.5 approximately 10 mg/kg/day. i.p., X 7), but did not change the activity of a high dose of 6-MP (40 approximately 80 mg/kg/day, i.p., X 7). The antitumor activity of thioinosine (6-MP riboside) was similarly increased by administration of butoctamide (100 mg/kg/day, i.p., X 7). On the other hand, concomitant administration of butoctamide with cyclophosphamide, methotrexate, mitomycin C or adriamycin had no effect on the activity of these anticancer drugs. In butoctamide (100 mg/kg/day, i.p., X 7)-treated mice, the antitumor activities of a single administration of 6-MP and cyclophosphamide were not increased. Butoctamide stimulated the hypoxanthine-guanine phosphoribosyltransferase activity and inhibited the xanthine oxidase activity of mouse liver, to a certain degree as compared to controls. Butoctamide may promote conversion from 6 MP to thioinosinic acid monophosphate to a biologically active state, rather than to thiouric acid or hypoxanthine which would be inactive.
D000577:Amides; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D006885:Hydroxybutyrates / Q000008:administration & dosage / Q000494:pharmacology*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D013868:Thioinosine / Q000627:therapeutic use; D014969:Xanthine Oxidase / Q000378:metabolism
D000577:Amides; D006885:Hydroxybutyrates; D013868:Thioinosine; C013857:butoctamide; D015122:Mercaptopurine; D014969:Xanthine Oxidase; D007041:Hypoxanthine Phosphoribosyltransferase