Nonlinear renal clearance of ultrafilterable platinum in patients treated with cis-dichlorodiammineplatinum (II).

Abstract

Nonlinear renal clearance of ultrafilterable platinum was observed in 5 of 7 patients given cis-dichlorodiammineplatinum (II) in doses of 50-140 mg/m2 by short-term infusion (2 h). Average renal clearance determined during and 24 h after infusion ranged from 100 to 543 ml/min and always exceeded creatinine clearance, suggesting that ultrafilterable platinum was renally secreted. Saturable tubular reabsorption was postulated on the basis that renal clearance was highest at peak plasma and urinary levels and fell as the levels declined. Although an overall relationship between dose and renal clearance was not apparent, one patient receiving the highest dose (140 mg/m2) had elevated average renal clearance (485 ml/min), probably associated with saturation of reabsorption, whereas a patient receiving 50 mg/m2 had the lowest average renal clearance (100 ml/min), indicating that either active secretion was lower, or tubular reabsorption was saturated. One patient also showed urine-flow-dependent changes in renal clearance. Four patients had transient rises in ultrafilterable platinum levels, which were attributed to changes in renal tubular reabsorption. The results suggest that renal clearance of ultrafilterable platinum is probably dependent on cis-DDP dose, urine flow rate, and individual variability in the extent of active secretion and tubular reabsorption. A sensitive HPLC method was applied and ultrafilterable platinum was detected in the plasma of all patients 24 h after infusion. Renal tubular reabsorption may result in prolonged plasma levels of ultrafilterable platinum, which could contribute to the drug's antitumour effect.