A patient with complete renal failure as a result of urothelial cell carcinoma-related nephrectomy of both kidneys received palliative chemotherapy with carboplatin and gemcitabine.
Hemodialysis effectively reduced plasma concentrations of dFdU. Furthermore, high concentrations of intracellular phosphorylated metabolites may be related to double-sided nephrectomy, resulting in poor tolerability of gemcitabine.
The patient received gemcitabine at 1,000 mg/m(2) followed by carboplatin at 100 mg. Shortly after, he underwent hemodialysis. The pharmacokinetics of gemcitabine and metabolites in plasma and in peripheral blood mononuclear cells were monitored.
Double-sided nephrectomy and hemodialysis had no influence on gemcitabine pharmacokinetics; however, a high exposure was seen for the main metabolite, difluordeoxyuridine (dFdU) (area under the concentration-time curve, 0-51 hours, 844 microg/ml.hour). During hemodialysis, plasma concentrations of dFdU were reduced by 50%. High concentrations of intracellular phosphorylated metabolites (gemcitabine triphosphate and dFdU triphosphate) were observed: 228 pmol/10(6) cells and 47 pmol/10(6) cells, respectively. The patient tolerated the regimen poorly; adverse events included grade 4 thrombocytopenia.
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