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

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


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
Issue number1
StatePublished - Jul 1981
Externally publishedYes

ASJC Scopus subject areas

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


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