PHARMACOKINETICS OF MINOMETHYL)-2-ISOPROPYL-1,3-DIOXOLANE]PLATINUM(II) IN RATS

The blood concentration-time profile, distribution, and excretion of c is-malonato[(4R, 5R)-4, -bis(aminomethyl)-2-isopropyl-1,3-dioxolane]pl atin (GAS 146665-77-2, SKI 2053R), a new potential anticancer agent, w ere investigated in rats after intravenous administration of C-14-SKI 2053R. After a single intravenous administration, the radioactivity of blood declined in a biexponential fashion with the initial half-lives of 0.42 h and 0.37 h and with the terminal half-lives of 68.67 h and 64.67 h in male and female rats, respectively. Radioactivity was distr ibuted very rapidly and extensively into all tissues except the centra l nervous system. The major amount of the radioactivity was found in t he gastrointestinal contents, urine, and organs of elimination at all time points. The distribution pattern of C-14-SKI 2053R observed by th e measurement of tissue concentrations was in accordance with that obs erved by whole-body autoradiography. The 0-7 days cumulative urinary a nd fecal recoveries of total radioactivity after a single dose were 83 .0 +/- 4.5 (mean +/- S.D.) and 11.3 +/- 1.0 % in male rats and 85.1 +/ - 2.6 and 11.3 +/- 2.3 % in female rats, respectively, resulting in to tal recoveries of 94.3 +/- 3.6 % in male rats and 96.3 +/- 1.1 % in fe male rats. The 0-24 h cumulative excretions of total radioactivity in the bile after a single dose were 8.7 +/- 0.4 and 15.8 +/- 3.5 % in ma le and female rats, respectively, showing a significant sex difference .