Studies on the pharmacokinetics and metabolism of cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) in the dog.

cis-Dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) (CHIP), a new antineoplastic platinum compound, was administered iv to dogs at a dose of 10 mg/kg. Thin-layer chromatography and high-pressure liquid chromatography (HPLC) were used to evaluate the pharmacokinetics of total Pt and of unchanged drug separated from the metabolites in urine. Both chromatographic procedures indicated a half-life of 0.3-0.5 hr for the unchanged CHIP (based on urinary excretion rates). Decay of total Pt after administration of CHIP was biphasic, with an alpha-half-life of 0.6 hr and a beta-half-life of 39.4 hrs. The long beta-half-life thus appears to be due to the retention of metabolites. Unchanged CHIP was separated from two groups of more polar Pt-containing metabolites by HPLC, as well as from another less polar Pt-containing complex that is found in urine of untreated dogs to which CHIP was added. AFter the administration of CHIP, with the simultaneous decline in its level, the proportion of the very polar Pt-containing metabolite(s) accumulated in the dog urine. Unlike cisplatin, CHIP did not bind to plasma proteins in vitro.