Inhibition of cis-diamminedichloroplatinum secretion by the human kidney with probenecid.
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 less than 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 less than 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.
D002945:Cisplatin / Q000097:blood / Q000627:therapeutic use / Q000652:urine*; D003404:Creatinine / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011339:Probenecid
D003404:Creatinine; D011339:Probenecid; D002945:Cisplatin