Pharmacokinetics of gemcitabine and metabolites in a patient with double-sided nephrectomy: a case report and review of the literature.
METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Koolen
Stijn L W
SL
Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands. s.koolen@nki.nl
Huitema
Alwin D R
AD
Jansen
Robert S
RS
van Voorthuizen
Theo
T
Beijnen
Jos H
JH
Smit
Willem M
WM
Schellens
Jan H M
JH
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000601:surgery; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects; D010166:Palliative Care; D006435:Renal Dialysis; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine