Distribution of Pt in the urine and kidney of the cisplatin treated rat.

The urinary and renal distribution of Pt following the administration of cis-dichlorodiammine platinum II (cisplatin) to adult male Wistar rats was studied by gel filtration and ion exchange chromatography. Several low molecular weight (LMW) Pt-containing fractions with the same chromatographic properties as those found in urine incubated with cisplatin are present in the kidney cytosol within 15 min of the administration of cisplatin. The concentration of Pt in these fractions decreases rapidly and after 4 h most of the Pt in the kidney cytosol is in a high molecular weight (HMW) fraction which contains 2 subfractions. The smaller fraction (mol. wt. = 20 000), but not the larger (mol. wt greater than 250 000), is also present in the urine of the cisplatin-treated rat, but neither fraction is present in urine incubated with cisplatin and neither is formed by the interaction of cisplatin or the urinary LMW Pt-containing fractions with kidney cytosol in vitro. It is suggested that the smaller fraction may be derived from the filtration and reabsorption of plasma protein-bound Pt, whereas the larger fraction is more likely to be formed exclusively within the kidney cell.