STUDIES ON PHARMACOKINETICS OF Z-2-AMINO- 5-CHLOROBENZOPHENONEAMIDINOHYDRAZONE(1) IN THE RAT

Model-independent and model-dependent pharmacokinetic parameters were determined from the course of total radioactivity in blood following s ingle i.v., p.o. and i.p. administration of two different doses of 2-a mino-5-chloro-C-14-benzophenoneamidinohydrazone (C-1). Following i.v. administration of C-14-1 the total radioactivity in blood exhibits dos e-dependent pharmacokinetics. After i.v. administration of 1,4 . 10(-6 ) mol . kg-1 C-14-1 the terminal half-life has been found with 7 h, wh ereas 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 whe n the dose is increased. Following p.o. administration of 1,4 . 10(-6) mol . kg-1 and 4,1 . 10(-4) mol . kg-1 C-14-1 the extent of absorptio n 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 C-14-1 the rate and extent of drug absorption i s high. The time course of total radioactivity in blood is similar to that after i.v. administration.