Pharmacokinetics of Gemcitabine and Metabolites in a Patient with Double-Sided Nephrectomy: A Case Report and Review of the Literature

Abstract

CASE 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. TREATMENT 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. RESULTS 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. CONCLUSION 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.