Measurement of plasma concentration of gemcitabine and its metabolite dFdU in hemodialysis patients with advanced urothelial cancer.
OBJECTIVE
We investigated the pharmacokinetics of gemcitabine and its metabolite in two male patients (52 and 56-year-old) with advanced urothelial cancer receiving hemodialysis three times a week.


METHODS
Gemcitabine, 1000 mg/m(2) in 100 ml of saline, was intravenously administered for 30 min. The concentration of gemcitabine and its metabolite 2',2'-difluorodeoxyuridine (dFdU) was measured at several given time points using a high-pressure liquid chromatography assay. Pharmacokinetic parameters were determined using the two-compartment modeling program.


RESULTS
Gemcitabine was rapidly eliminated from plasma even in patients with renal dysfunction. No obvious differences in pharmacokinetic parameters such as the t(1/2), AUC and C(max) of gemcitabine were observed between the patients on hemodialysis and those with normal renal function in previous reports. On the other hand, dFdU showed a sustained level until hemodialysis was initiated. Hemodialysis could reduce the plasma dFdU level by approximately 50%.


CONCLUSIONS
According to the previous information, no dose modification of gemcitabine may be required for patients with renal impairment or hemodialysis. However, gemcitabine should be given with caution because only limited information is available, and the clinical effect of sustained and/or accumulated dFdU is unknown.
Masumori
Naoya
N
Department of Urology, Sapporo Medical University, S1, W16, Chuo-ku, Sapporo 060-8543, Japan. masumori@sapmed.ac.jp
Kunishima
Yasuharu
Y
Hirobe
Megumi
M
Takeuchi
Motoi
M
Takayanagi
Akio
A
Tsukamoto
Taiji
T
Itoh
Tatsuya
T
D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000627:therapeutic use; D019540:Area Under Curve; D001859:Bone Neoplasms / Q000556:secondary; D015653:Cystectomy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D017809:Fatal Outcome; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood* / Q000628:therapy*; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000150:complications / Q000628:therapy; D014516:Ureteral Neoplasms / Q000097:blood* / Q000628:therapy; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000628:therapy*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003841:Deoxycytidine; C084565:2',2'-difluoro-2'-deoxyuridine; D000093542:Gemcitabine