The blood concentration-time profile, distribution, and excretion of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3-dioxolane]platinum(II) (CAS 146665-77-2, SKI 2053R), a new potential anticancer agent, were investigated in rats after intravenous administration of 14C-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 distributed very rapidly and extensively into all tissues except the central nervous system. The major amount of the radioactivity was found in the gastrointestinal contents, urine, and organs of elimination at all time points. The distribution pattern of 14C-SKI 2053R observed by the measurement of tissue concentrations was in accordance with that observed by whole-body autoradiography. The 0-7 days cumulative urinary and 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 total recoveries of 94.3 +/- 3.6% in male rats and 96.3 +/- 1.1% in female 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 male and female rats, respectively, showing a significant sex difference.