Plasma free platinum pharmacokinetics in patients treated with high dose carboplatin

Abstract

Plasma free platinum (less than 50,000 mol. wt) pharmacokinetics have been studied in eight patients treated with high-dose (800-1600 mg/m2) carboplatin as a 1 h infusion with moderate hydration. Following the infusion, levels decayed biphasically with half-lives (means +/- S.D.) of 83 +/- 15 min and 6.1 +/- 2.8 h. The plasma free platinum area under the concentration vs. time curve (AUC) at 1600 mg/m2 in five patients was 23 +/- 2 mg carboplatin/ml.min. Comparison with data at conventional doses (less than or equal to 500 mg/m2) gave no indication of non-linear kinetics. Total body clearance of free platinum was found to correlate with glomerular filtration rate (r = 0.769, P = 0.03), and haematological toxicity, white cell nadir and duration of thrombocytopenia, correlated with plasma free platinum AUC (r = 0.784, P = 0.02 and r = 0.885, P = 0.01, respectively). Persistence of platinum was demonstrated in tissues removed at autopsy from a patient who had received carboplatin 14 days earlier. Highest platinum levels were found in the liver, kidney, skin and small cell lung tumour.