Enhancement by tetrahydrouridine (NSC-112907) of the oral activity of 5-azacytidine (NSC-102816) in L1210 leukemic mice.
5-Azacytidine is more active when administered parenterally than orally in the treatment of L1210 leukemic mice. Oral coadministration of tetrahydrouridine, a pyrimidine nucleoside deaminase inhibitor with no intrinsic antitumor activity, greatly increases the oral activity of 5-azacytidine. 5-azacytidine (or cytotoxic equivalent) blood levels in BDF mice are much higher after oral administration of the 5-azacytidine-tetrahydrouridine combination than when 5-azacytidine is administered alone by the same route. The therapeutic results (L1210 leukemia) achieved with the oral combination are similar to those observed with parenteral 5-azacytidine alone.
D000284:Administration, Oral; D000818:Animals; D001374:Azacitidine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004357:Drug Synergism; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D013767:Tetrahydrouridine / Q000494:pharmacology; D014529:Uridine / Q000031:analogs & derivatives*
D013767:Tetrahydrouridine; D001374:Azacitidine; D014529:Uridine