Medical Oncology and Tumor Pharmacotherapy

, Volume 5, Issue 3, pp 153–158 | Cite as

Pharmacokinetics ofcis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV (iproplatinum, chip) in patients with normal and impaired renal function and following intraperitoneal administration

  • D. J. Kerr
  • M. Harding
  • J. G. Farmer
  • J. Amarin
  • R. G. Blackie
  • S. J. Harland
  • S. B. Kaye
Original Articles


CHIP is a quadrivalent platinum (Pt) complex, introduced clinically as a less toxic alternative tocis-platinum. The drug’s major route of excretion is via the kidneys, and in this study the pharmacokinetics of unchanged CHIP, filterable Pt and total Pt have been determined following intravenous administration to patients with a range of renal function. Total Pt and filterable Pt in plasma decayed biexponentially and was fitted to a two-compartment model, whereas unchanged CHIP declined monoexponentially and was best fitted to a one-compartment model, according to Akaike’s information criteria. There is a correlation between the unchanged CHIP clearance and51Cr-EDTA clearance. The pharmacokinetics of CHIP was determined following intraperitoneal (i.p.) administration (dose, 150–300 mg m−2 4 h dwell time) and a regional advantage (peritoneal peak concentration/plasma peak concentration) of approximately 30 fold was seen. It is likely that the dose of CHIP will need to be reduced in patients with impaired renal function, and the use of i.p. CHIP in ovarian carcinoma warrants further study.

Key words

CHIP pharmacokinetics Intraperitoneal 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Highby D J, Wallace H J Jr, Alberts D, Holland J F: Diamminedichloro platinum in the chemotherapy of testicular tumours.J Urol 112, 110 (1971).Google Scholar
  2. 2.
    Wiltshaw E, Carr T:Cis-platinum(II) diamminedichloride clinical experiences of the Royal Marsden Hospital and Institute of Cancer Research.Recent Results Cancer Res 48, 178 (1974).Google Scholar
  3. 3.
    Prestyako A W, D’Aoust J C, Issell B F, Crooke S T: Cisplatin (cis-diammine dichloro platinum II).Cancer Treat Rev 6, 17 (1979).CrossRefGoogle Scholar
  4. 4.
    Creaven P J, Madjewicz S, Lakshmi P, Mittelman A, Pontes E, Spaulding M, Arbuck S and Solomon J: Phase I clinical trial ofcis-dichloro-trans-dihydroxy-bis-isopropylamine platinum (IV) (CHIP).Cancer Treat Rep 67, 795 (1983).PubMedGoogle Scholar
  5. 5.
    Pendyala L, Greco W, Cowens J W, Madajewicz S, Creaven P J: Pharmacokinetics of CHIP in patients with advanced cancer.Cancer Chemother Pharmac 11, 23 (1983).Google Scholar
  6. 6.
    Pendyala L., Madajewicz S., Lele S B, Arbuck S G, Creaven P J: Evaluation of the nephrotoxicity of iproplatin (CHIP) in comparison to cisplatin by the measurement of urinary enzymes.Cancer Chemother Pharmac 15, 203 (1985).Google Scholar
  7. 7.
    Pendyala L, Madajewicz S, Creaven P J: Effect of renal function impairment on iproplatinum pharmacokinetics and relation to toxicity.Cancer Res 45, 5936 (1985).PubMedGoogle Scholar
  8. 8.
    Harland S J, Newell D R, Siddik Z H, Chadwick R, Calvert A H, Harrap K R: Pharmacokinetics of cis-diammine-1,l-cyclobutane dicarboxylate platinum (II) in patients with normal and impaired renal function.Cancer Res 44, 1693 (1984).PubMedGoogle Scholar
  9. 9.
    Egorin M J, Van Echo D A, Tipping S J, Olman E A, Whitacre M Y, Thompson B W, Aisner J: Pharmacokinetics and dosage reduction of cis-diammine (1,1-cyclobutane dicarboxylate) platinum in patients with impaired renal function.Cancer Res 44, 5432 (1984).PubMedGoogle Scholar
  10. 10.
    Howell S B, Pfeifle C E, Wung W E, Olshen R A, Lucas W E, Yon J L, Green M R: Intraperitoneal cisplatin with systemic thiosulfate protection.Ann intern Med 97, 845 (1982).PubMedGoogle Scholar
  11. 11.
    Ozols R, Locker G, Doroshow J: Pharmacokinetics of adriamycin and tissue penetration in murine ovarian cancer.Cancer Res 29, 3209 (1979).Google Scholar
  12. 12.
    Sutherland R M, Eddy H A, Bareham B, Reich K, Vanantwerp D: Resistance to adriamycin in multicellular spheroids.Int J. Radiat Oncol biol Phys 5, 1225 (1979).PubMedGoogle Scholar
  13. 13.
    Kerr D J, Wheldon T E, Kerr A M, Freshney R I, Kaye S B: The effect of adriamycin and 4′-deoxydoxorubicin on cell survival of human lung tumour cells grown in monolayers and as spheroids.Br J Cancer 54, 423 (1986).PubMedGoogle Scholar
  14. 14.
    Chantier C, Garnett E S, Parsons V, Veall N: Glomerular filtration rate measurement in man by the single injection method using5lCr-EDTA.Clin Sci 37, 169 (1969).Google Scholar
  15. 15.
    Reece P A, McCall J T, Powis G, Richardson R L. Sensitive high-performance liquid Chromatographic assay for platinum in plasma ultrafiltrate.J Chromat 306, 417 (1984).CrossRefGoogle Scholar
  16. 16.
    Bevington P R:Data Reduction and Error Analysis for the Physical Sciences, pp. 235–236. New York, McGraw-Hill (1969).Google Scholar
  17. 17.
    Gormley P E, Bull J M, LeRoy A F, Cysyk R: Kinetics of cis-dichlorodiammine platinum.Clin Pharmac Ther 25, 351 (1979).Google Scholar
  18. 18.
    Speyer J L, Myers C E: The use of peritoneal dialysis for delivery of chemotherapy to intraperitoneal malignancies.Recent Res Cancer Res 74, 164 (1980).Google Scholar
  19. 19.
    Ozols R F, Young R C, Speyer J L, Sugarbaker P H, Green R, Jenkins J, Myers C E: Phase I and pharmacologie studies of adriamycin administered intraperitoneally to patients with ovarian cancer.Cancer Res 42, 4265 (1982).PubMedGoogle Scholar
  20. 20.
    Howell S B, Chu B C F, Wung W., Metha B, Mendelsohn J: Long duration intracavitary infusion of methotrexate with systemic leucovorin protection in patients with malignant effusions.J clin. Invest 67, 1167 (1981).CrossRefGoogle Scholar
  21. 21.
    King M E, Howell S B. Intraperitoneal cytarabine therapy in ovarian carcinoma.J clin Oncol 2, 662 (1984).PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1988

Authors and Affiliations

  • D. J. Kerr
    • 1
  • M. Harding
    • 1
  • J. G. Farmer
    • 2
  • J. Amarin
    • 1
  • R. G. Blackie
    • 1
  • S. J. Harland
    • 1
  • S. B. Kaye
    • 1
  1. 1.University Department of Medical OncologyGlasgow University
  2. 2.Department of ChemistryUniversity of EdinburghUSA

Personalised recommendations