Pharmacokinetic considerations in evaluating the effects of tetrahydrouridine on 5-azacytidine chemotherapy in L1210 leukemic mice.
The pharmacokinetics of 5-azacytidine (5-azaCR) and tetrahydrouridine (THU) were considered in evaluating the effect of THU on chemotherapy with 5-azaCR in L1210 leukemia mice. The administration of three different dose levels of THU and 5-azaCR ip in either a 6- or 72-hour infusion gave minimal increases in therapeutic effect. At the high-dose combinations (except in the 72-hour infusion), THU appeared to enhance toxicity. Toxicity, however, occurred only after exceeding a theoretic plasma concentration for 5-azaCR of 61 microgram/ml. THU was effective in increasing the excretion of 5-azaCR by sixfold and in altering its urinary metabolites when given simultaneously with or up to 1 hour prior to 5-azaCR.
D000818:Animals; D001374:Azacitidine / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D007263:Infusions, Parenteral; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D013767:Tetrahydrouridine / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D014529:Uridine / Q000031:analogs & derivatives*
D013767:Tetrahydrouridine; D001374:Azacitidine; D014529:Uridine