Document Detail


Inhibition of cis-diamminedichloroplatinum secretion by the human kidney with probenecid.
MedLine Citation:
PMID:  6540140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
C Jacobs; C N Coleman; L Rich; K Hirst; M W Weiner
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  44     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1984 Aug 
Date Detail:
Created Date:  1984-08-29     Completed Date:  1984-08-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3632-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cisplatin / blood,  therapeutic use,  urine*
Creatinine / metabolism
Humans
Kidney / drug effects,  physiopathology*
Metabolic Clearance Rate / drug effects
Neoplasms / drug therapy*,  physiopathology
Probenecid / diagnostic use*
Grant Support
ID/Acronym/Agency:
CA-05838/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
15663-27-1/Cisplatin; 57-66-9/Probenecid; 60-27-5/Creatinine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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