[Pharmacokinetic studies of dFdC (2',2'-difluorodeoxycytidine), ara-C and BH-AC (N4-behenoyl ara-C) in experimental animals].
dFdC (2',2'-difluorodeoxycytidine; LY 188011), a new analogue of ara-C, which contains fluorines in the sugar moiety, has shown a wider antitumor spectrum and has effective to solid tumors, as compared with ara-C. The pharmacokinetic behavior of dFdC was compared with that of sera-C or BH-AC (N4-behenoyl ara-C) using experimental animals. The results were as follows. 1. Plasma levels (rabbits): The half-lives of dFdC were longer than those of ara-C. The peak level of ara-C, which derived from BH-AC, was not so high but continued for relatively a long time. 2. Tissue levels (S.180 tumor bearing mice): dFdC levels were high in the spleen and thymus, tumor, testis and muscle, and persisted longer than ara-C. The levels of ara-C derived from BH-AC were low, but persisted for a long time. 3. Inactivation: The grade of inactivation of dFdC to dFdU was observed as same as that of ara-C to ara-U. dFdC was rapidly phosphorylated to dFdCTP in tumor cells, and dFdCTP accumulated higher, when compared with ara-CTP. Clinically, the determinations of unchanged drug levels in the plasma, and the dFdCTP, ara-CTP and dCTP levels in tumor tissue seemed to be important.
Okamoto
M
M
Dept. of Bacteriology, School of Dental Medicine, Tsurumi University.
Fujita
H
H
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006207:Half-Life; D008099:Liver / Q000378:metabolism; D051379:Mice; D011817:Rabbits; D012513:Sarcoma, Experimental / Q000378:metabolism*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003561:Cytarabine; D003841:Deoxycytidine; C015019:enocitabine; D000093542:Gemcitabine