Inhibition of cis-diamminedichloroplatinum secretion by the human kidney with probenecid

C. Jacobs, C. N. Coleman, L. Rich, K. Hirst, M. W. Weiner

Research output: Contribution to journalArticle

Abstract

The renal handling of cis-diamminedichloroplatinum (CP) was investigated by measuring the renal clearance of creatinine, inulin, and free platinum in ten cancer patients. Free platinum clearances exceeded the glomerular filtration rate in all time periods. For example, at 1 to 2 hr, the mean clearance of free platinum was 224 ± 32 (S.E.) ml/min compared to a mean creatinine clearance of 94 ± 15 ml/min or a mean inulin clearance of 94 ± 17 ml/min (p <0.01), indicating secretion of CP or a metabolite. Seven additional cancer patients were treated with probenecid prior to CP. Fractional platinum clearances, calculated as a ratio of free platinum clearance to creatinine clearance, were reduced significantly in the probenecid-treated group (158 ± 17%) compared to controls (270 ± 57%) (p = 0.03). Fractional platinum clearances, calculated as a ratio of free platinum clearance to inulin clearance, were also significantly reduced in the treated group (154 ± 14%) compared to controls (271 ± 47%) (p = 0.04). These results suggest that cisplatin is secreted by the human kidney, and this can be inhibited by probenecid. Such maneuvers may be helpful in improving the therapeutic index of this important chemotherapeutic agent.

Original languageEnglish (US)
Pages (from-to)3632-3635
Number of pages4
JournalCancer Research
Volume44
Issue number8
Publication statusPublished - 1984
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Jacobs, C., Coleman, C. N., Rich, L., Hirst, K., & Weiner, M. W. (1984). Inhibition of cis-diamminedichloroplatinum secretion by the human kidney with probenecid. Cancer Research, 44(8), 3632-3635.