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Plasma free platinum pharmacokinetics in patients treated with high dose carboplatin

Lookup NU author(s): Professor Herbie Newell, Professor Alan Calvert

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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.

Publication metadata

Author(s): Newell DR, Siddik ZH, Gumbrell LA, Boxall FE, Gore ME, Smith IE, Calvert AH

Publication type: Article

Publication status: Published

Journal: European Journal of Cancer & Clinical Oncology

Year: 1987

Volume: 23

Issue: 9

Pages: 1399-1405

Print publication date: 01/09/1987

ISSN (print): 0277-5379

ISSN (electronic): 1879-0852

URL: http://dx.doi.org/10.1016/0277-5379(87)90126-X

DOI: 10.1016/0277-5379(87)90126-X

PubMed id: 3315699

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