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

S.L.W. Koolen, A.D.R. Huitema, R.S. Jansen, T. van Voorthuizen, J.H. Beijnen, W.M Smit, J.H.M. Schellens

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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 mu g/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/106 cells and 47 pmol/106 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. The Oncologist 2009; 14:944-948
Original languageUndefined/Unknown
Pages (from-to)944-948
Number of pages5
JournalOncologist
Volume14
Issue number9
Publication statusPublished - 2009

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ISI:000270042200010

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