Disposition and distribution of platinum following parenteral administration of cis-dichlorodiammineplatinum(II) to animals

Abstract

After iv administration of cis-dichlorodiammineplatinum(II) (cis-platinum) to animals, plasma levels of platinum decline in a biphasic manner, with a distribution phase (alpha) half-life of minutes and an elimination phase (beta) half-life of days. Urinary excretion of platinum is extensive on the first day after drug administration with a final urinary recovery of 70%--90% of the administered dose. Platinum is initially distributed to nearly all tissues with the highest levels appearing in kidney, liver, ovary, uterus, skin, and bone. There is no preferential uptake of platinum into tumor, although the presence of a tumor may alter the rate of platinum excretion and the extent of whole-body retention. No effect is seen on hepatic microsomal drug metabolism after ip administration of cis-platinum to rats. Platinum is excreted more rapidly from hydrated animals than from controls although total urinary recovery of platinum is nearly equal in both groups. Most analogs of cis-platinum appear to follow the same elimination and distribution patterns as cis-platinum itself.