Pharmacokinetics and protein binding of cis-dichlorodiammine platinum (II) administered as a one hour or as a twenty hour infusion |
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| Authors: | John J. Gullo Charles L. Litterst Patrick J. Maguire Branimir I. Sikic Daniel F. Hoth Paul V. Woolley |
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| Affiliation: | (1) Department of Medicine, Division of Medical Oncology, Georgetown University Schools of Medicine and Dentistry, 20007 Washington, D.C., USA;(2) Department of Pharmacology (PVW), Georgetown University Schools of Medicine and Dentistry, 20007 Washington, D.C., USA;(3) Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, 20007 Washington, D.C., USA;(4) Laboratory of Toxicology, National Cancer Institute, National Institutes of Health, 20205 Bethesda, Maryland, USA;(5) Present address: 725 Irving Avenue, Suite 302, 13210 Syracuse, New York, USA;(6) Present address: Department of Medicine, Division of Medical Oncology, Stanford University Medical Center, Palo Alto, California, USA;(7) Georgetown University Hospital, 3800 Reservoir Road, N.W., Room 2100 West, 20007 Washington, D.C., USA |
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| Abstract: | 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  -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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