Plasma free platinum pharmacokinetics in patients treated with high dose carboplatin

Plasma free platinum (< 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 (x̄ ± 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 (≤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.