PHARMACOKINETICS, TISSUE DISTRIBUTION, AND EXCRETION OF MINOMETHYL)-2-ISOPROPYL-1,3-DIOXOLANE]PLATINUM(II) IN DOGS

The pharmacokinetics, tissue distribution, and excretion of cismalonat o[(4R,5R)-4,5-bis(aminomethyl)-2- 1,3-dioxolane]platinum(II) (SKI 2053 R), a new potential anticancer agent, were investigated in dogs after a single intravenous administration of [C-14]SKI 2053R (7 mg/kg, 100 m u Ci/kg). Total radioactivity in the plasma and ultrafiltrable plasma declined in a biexponential fashion with the initial half-lives of 0.6 3 +/- 0.05 hr (mean +/- SD) and 0.53 +/- 0.05 hr, and with the termina l half-lives of 51.08 +/- 3.26 hr and 15.19 +/- 3.75 hr, respectively. Radioactivity was well distributed into all tissues except the centra l nervous system. The majority of the radioactivity was found in the g astrointestinal contents, urine, and organs of elimination at all time points. The distribution pattern of [C-14]SKI 2053R in the whole-body autoradiograms was consistent with that observed by the measurement o f tissue concentrations, The 0-7 days cumulative urinary and fecal rec overies of total radioactivity were 87.30 +/- 2.93% and 8.68 +/- 1.30% , respectively, resulting in a total recovery of 95.98 +/- 1.61% of th e administered dose, A large portion of [C-14]SKI 2053R was distribute d into the cellular fraction of mouse or rat blood, but was not into t hat of dog or human blood in vitro. The in vitro and in vivo binding o f [C-14]SKI 2053R to plasma protein was minimal to moderate.