ABSTRACT
Model-independent and model-dependent pharmacokinetic parameters were determined from the course of total radioactivity in blood following single i.v., p.o. and i.p. administration of two different doses of Z-2-amino-5-chloro-14C-benzophenoneamidinohydrazone (14C-1). Following i.v. administration of 14C-1 the total radioactivity in blood exhibits dose-dependent pharmacokinetics. After i.v. administration of 1,4.10(-6) mol.kg-1 14C-1 the terminal half-life has been found with 7 h, whereas this value is 32 h after administration of 4,4.10(-5) mol.kg-1 to female rats and 18 h after administration of 3,1.10(-5) mol.kg-1 to male rats. The apparent volume of distribution increases when the dose is increased. Following p.o. administration of 1,4.10(-6) mol.kg-1 and 4,1.10(-4) mol.kg-1 14C-1 the extent of absorption amounts to 21 and 59%, respectively. This effect of dose is related to the dose-dependent prolongation of gastrointestinal passage. After i.p. administration of 14C-1 the rate and extent of drug absorption is high. The time course of total radioactivity in blood is similar to that after i.v. administration.
