INHIBITION OF CIS-DIAMMINEDICHLOROPLATINUM SECRETION BY THE HUMAN-KIDNEY WITH PROBENECID

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (8) , 3632-3635
Abstract
The renal handling of cis-diamminedichloroplatinum (CP) was investigated by measuring the renal clearance of creatinine, inulin and free Pt in 10 cancer patients. Free Pt clearances exceeded the glomerular filtration rate in all time periods. For example at 1-2 h, the mean clearance of free Pt was 224 .+-. 32 (SE) ml/min compared to a mean creatinine clerance 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 Pt clearances, calculated as a ratio of free Pt clearance to creatinine clearance, were reduced significantly in the probenecid-treated group (158 .+-. 17%) compared to controls (270 .+-. 57%) (P = 0.03). Fractional Pt clearances, were also significantly reduced in the treated group (154 .+-. 14%) compared to controls (271 .+-. 47%) (P = 0.04). Cisplatin is apparently secreted by the human kidney, and can be inhibited by probenecid. Such maneuvers may be helpful in improving the therapeutic index of this important chemotherapeutic agent.