Cisplatin disposition in children and adolescents with cancer

William R. Crom, William E. Evans, Charles B. Pratt, Neil Senzer, Marilyn Denison, Alexander A. Green, F. Ann Hayes, Gary C. Yee

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Abstract

The disposition of cisplatin was evaluated in 28 children and adolescents with cancer, as part of a phase II clinical trial. Patients received either 30 mg/m2 (11) or 90 mg/m2 (17) of cisplatin as a 6-h IV infusion. Serum samples and divided urine collections were obtained over 48 h following completion of the cisplatin infusion, and were assayed in duplicate for total platinum by atomic absorption spectrophotometry. Serum samples obtained up to 4 h after three cisplatin infusions were assayed for parent (free) cisplatin following ultrafiltration. The mean (±SE) elimination half-life of free cisplatin in serum was 1.3 (±0.4) h. Serial serum concentrations of total platinum following 90 mg/m2 dosages were adequately described by a biexponential equation. The mean (±SE) serum T1/2α of total platinum was 0.42 (±0.10) h and the mean (±SE) T1/2β was 44.43 (±8.24) h. The intercompartment distribution rate constants of a two-compartment kinetic model indicate extensive tissue accumulation of total platinum, with a rate of transport into tissue compartments (K12) that is about six times the rate of transport out of tissues (K21). The mean (±SE) renal clearance of total platinum from 0-3 h was 37.36 (±11.96) ml/min/m2 and 35.8 (±13.6) ml/min/m2 for the 30 mg/m2 and 90 mg/m2 groups, respectively. This value decreased to 3.25 (±0.94) and 2.16 (±0.4) ml/min/m2 for the two groups by the 6-12 h interval, and remained between 1 and 3 ml/min/m2 for the duration of the observation period. The ratio of total plantinum clearance to creatinine clearance decreased significantly(P<0.05) beginning 3 h post-infusion. The change in renal clearance of total platinum is apparently a function of two independent first-order processes for renal clearance of parent drug and cisplatin metabolites.

Original languageEnglish (US)
Pages (from-to)95-99
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume6
Issue number1
DOIs
StatePublished - Jul 1981

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ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Crom, W. R., Evans, W. E., Pratt, C. B., Senzer, N., Denison, M., Green, A. A., Ann Hayes, F., & Yee, G. C. (1981). Cisplatin disposition in children and adolescents with cancer. Cancer Chemotherapy and Pharmacology, 6(1), 95-99. https://doi.org/10.1007/BF00253017