STUDIES ON THE PHARMACOKINETICS AND METABOLISM OF CIS-DICHLORO-TRANS-DIHYDROXY-BIS-ISOPROPYLAMINE PLATINUM(IV) IN THE DOG

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 66  (3) , 509-516
Abstract
Cis-Dichloro-trans-dihydroxy-bis-isopropylamine platinum(IV) (CHIP), a new antineoplastic Pt compound, was administered i.v. to dogs at a dose of 10 mg/kg. TLC 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 [t1/2] of 0.3-0.5 h for the unchanged CHIP (based on urinary excretion rates). Decay of total Pt after administration of CHIP was biphasic, with an .alpha.-t1/2 of 0.6 h and a .beta.-t1/2 of 39.4 h. The long .beta.-t1/2 thus appears to be due to the retention of metabolites. Unchanged CHIP was separated from 2 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.