The mechanism of renal clearance of cisplatin (cis-dichlorodiammine platinum ii) and its modification by furosemide and probenecid.
When isolated rat kidneys are perfused with 30 microM cisplatin there is net tubular transport of platinum, resulting in excretion of platinum at a rate 125% of the rate attributable to glomerular filtration alone. Probenecid and furosemide are drugs which have been reported to protect against cisplatin nephrotoxicity, by unknown mechanisms. When probenecid 0.3 mM is included in the perfusate net transport of platinum is increased to 200% of that accounted for by glomerular filtration alone. Increasing the concentration of probenecid to 3.0 mM does not significantly further increase the rate of excretion of platinum. The inclusion of furosemide 0.3 mM in the perfusate has no effect on the net tubular transport of platinum. However, at 3.0 mM furosemide causes a decrease in the net platinum transport and only 93% of platinum filtered at the glomerulus appears in the urine. Thin-layer chromatography revealed the presence of at least three platinum compounds in the urine in addition to cisplatin. We conclude that the renal excretion of cisplatin and its transformation products, even in this model system, is a complex process involving glomerular filtration, tubular excretion and tubular reabsorption.
D000818:Animals; D002945:Cisplatin / Q000378:metabolism*; D005665:Furosemide / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011339:Probenecid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005665:Furosemide; D011339:Probenecid; D002945:Cisplatin