A study of the pharmacokinetics of single i. v. administration of a dose of 100 mg.kg-1 of fazarabine to control rats and rats with hepatic cirrhosis has demonstrated in rats with hepatic cirrhosis a prolongation of the parameters t 0.5β and MRT to the level of the values of these parameters calculated on a two-compartmental model of control rats after i. v. administration of a double dose, i. e., 200 Ag.kg-1 fazarabine. Hepatic cirrhosis in rats caused a decrease in the Cltot value of fazarabine by 46% as compared with controls. These studies only demonstrate changes in the values of kinetic parameters of ARA-AC due to a pathologically changed function in the rat liver, which results in a necessary decrease of the dose of l-β-D-arabinofuranosyl-5-azacytosine to one half in the case of its i. v. administration when hepatic cirrhosis is involved. Further preclinical tests of the drug will be necessary to secure the optimal dosing of l-β-D-arabinofuranosyl-5-azacytosine.
Pharmacokinetics l-β-D-arabinofuranosyl-5-azacytosine in the model of rats with chronic mutilated liver
