In vivo studies on high-dose 1-beta-D-arabinofuranosylcytosine (HDara-C) and 1-beta-D-arabinofuranosyluracil (ara-U) with respect to pharmacokinetics, cell kinetics, and cytotoxicity in a rat myelocytic leukemia model (BNML).
From the current studies it can be concluded that comparing the ara-C catabolism to ara-U in leukemic rats and leukemic patients, this process is about 100 times more pronounced in human leukemic cells. The low deaminase activity in leukemic rats probably explains the slow plasma ara-C disappearance curve in the BNML. No cytotoxic effect of ara-U with respect to LCFU-S reduction could be observed, nor did ara-U enhance the cytotoxic effect ara-C in the BNML. These studies have increased the understanding of the relation between ara-C, ara-U plasma levels and deaminase activity.
D000818:Animals; D001086:Arabinofuranosyluracil / Q000097:blood* / Q000494:pharmacology; D002453:Cell Cycle; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000097:blood* / Q000627:therapeutic use; D003564:Cytidine Deaminase; D004195:Disease Models, Animal; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000188:drug therapy; D009700:Nucleoside Deaminases / Q000097:blood; D051381:Rats; D014529:Uridine / Q000031:analogs & derivatives*
D003561:Cytarabine; D001086:Arabinofuranosyluracil; D009700:Nucleoside Deaminases; D003564:Cytidine Deaminase; C011530:deoxycytidine deaminase; D014529:Uridine