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  • Title: Pharmacokinetic considerations in evaluating the effects of tetrahydrouridine on 5-azacytidine chemotherapy in L1210 leukemic mice.
    Author: Kelly CJ, Gaudio L, Yesair DW, Schoenemann PT, Wodinsky I.
    Journal: Cancer Treat Rep; 1978 Jul; 62(7):1025-32. PubMed ID: 80268.
    Abstract:
    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.
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