title: Measurement of plasma concentration of gemcitabine and its metabolite dFdU in hemodialysis patients with advanced urothelial cancer.
abstract: 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.
authors.affiliation: Department of Urology, Sapporo Medical University, S1, W16, Chuo-ku, Sapporo 060-8543, Japan. masumori@sapmed.ac.jp
authors.forename: Naoya
authors.initials: N
authors.lastname: Masumori
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Kunishima
authors.forename: Megumi
authors.initials: M
authors.lastname: Hirobe
authors.forename: Motoi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Akio
authors.initials: A
authors.lastname: Takayanagi
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Itoh
mesh_terms: 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
chemical_list: D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003841:Deoxycytidine; C084565:2',2'-difluoro-2'-deoxyuridine; D000093542:Gemcitabine