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Pharmacokinetics and protein binding of cis-dichlorodiammine platinum (II) administered as a one hour or as a twenty hour infusion

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  • Pharmacokinetics of Cisplatin
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Summary

The pharmacokinetics of cis-dichlorodiamminoplatinum (II) (cisplatin) have been studied in seven patients, of whom four received the drug as a one hour infusion and three received it as a 20 h infusion. The patients receiving the drug over one hour exhibited biphasic clearance of total platinum with a rapid initial phase (8.7–22.5 min) and a prolonged second phase (30.5–106 h). Free (ultrafilterable) cisplatin was readily detectable in this group and was rapidly cleared (half-life about 22 min). The volume of distribution of the drug was 50.3–65.6 liters and it was 26.6–50% excreted in the urine in 48h. In the patients receiving the 20 h infusion, a more complex plasma elimination curve was seen, with the appearance of a secondary peak. Free drug was not detectable in these patients and they showed less urinary excretion (21.4–25.9% at 48 h) than the one hour group. Cisplatin was bound to several plasma proteins, including albumin, transferrin, and γ-globulin. The data indicate that cisplatin is retained in the body more extensively after a 20 h infusion than after a one hour infusion.

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Author notes

  1. John J. Gullo

    Present address: , 725 Irving Avenue, Suite 302, 13210, Syracuse, New York, USA

  2. Branimir I. Sikic

    Present address: Department of Medicine, Division of Medical Oncology, Stanford University Medical Center, Palo Alto, California, USA

Authors and Affiliations

  1. Department of Medicine, Division of Medical Oncology, Georgetown University Schools of Medicine and Dentistry, 20007, Washington, D.C., USA

    John J. Gullo, Patrick J. Maguire, Branimir I. Sikic, Daniel F. Hoth & Paul V. Woolley

  2. Department of Pharmacology (PVW), Georgetown University Schools of Medicine and Dentistry, 20007, Washington, D.C., USA

    John J. Gullo, Patrick J. Maguire, Branimir I. Sikic, Daniel F. Hoth & Paul V. Woolley

  3. Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, 20007, Washington, D.C., USA

    John J. Gullo, Patrick J. Maguire, Branimir I. Sikic, Daniel F. Hoth & Paul V. Woolley

  4. Laboratory of Toxicology, National Cancer Institute, National Institutes of Health, 20205, Bethesda, Maryland, USA

    Charles L. Litterst

Authors
  1. John J. Gullo
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  5. Daniel F. Hoth
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  6. Paul V. Woolley
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Gullo, J.J., Litterst, C.L., Maguire, P.J. et al. Pharmacokinetics and protein binding of cis-dichlorodiammine platinum (II) administered as a one hour or as a twenty hour infusion. Cancer Chemother. Pharmacol. 5, 21–26 (1980). https://doi.org/10.1007/BF00578558

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  • DOI: https://doi.org/10.1007/BF00578558

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