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 journalArticle

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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

Fingerprint

Cisplatin
Platinum
Neoplasms
Serum
Tissue
Kidney
Atomic Spectrophotometry
Urine Specimen Collection
Phase II Clinical Trials
Ultrafiltration
Spectrophotometry
Metabolites
Half-Life
Rate constants
Creatinine
Observation
Kinetics
Pharmaceutical Preparations

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., ... 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

Cisplatin disposition in children and adolescents with cancer. / Crom, William R.; Evans, William E.; Pratt, Charles B.; Senzer, Neil; Denison, Marilyn; Green, Alexander A.; Ann Hayes, F.; Yee, Gary C.

In: Cancer Chemotherapy and Pharmacology, Vol. 6, No. 1, 07.1981, p. 95-99.

Research output: Contribution to journalArticle

Crom, WR, Evans, WE, Pratt, CB, Senzer, N, Denison, M, Green, AA, Ann Hayes, F & Yee, GC 1981, 'Cisplatin disposition in children and adolescents with cancer', Cancer Chemotherapy and Pharmacology, vol. 6, no. 1, pp. 95-99. https://doi.org/10.1007/BF00253017
Crom WR, Evans WE, Pratt CB, Senzer N, Denison M, Green AA et al. Cisplatin disposition in children and adolescents with cancer. Cancer Chemotherapy and Pharmacology. 1981 Jul;6(1):95-99. https://doi.org/10.1007/BF00253017
Crom, William R. ; Evans, William E. ; Pratt, Charles B. ; Senzer, Neil ; Denison, Marilyn ; Green, Alexander A. ; Ann Hayes, F. ; Yee, Gary C. / Cisplatin disposition in children and adolescents with cancer. In: Cancer Chemotherapy and Pharmacology. 1981 ; Vol. 6, No. 1. pp. 95-99.
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