Pharmacokinetics of gemcitabine and 2',2'-difluorodeoxyuridine in a patient with ascites.
Gemcitabine (dFdC) is a prodrug that undergoes metabolism by cytidine deaminase to form an inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU). The pharmacokinetics of dFdC and dFdU have been studied; however, their disposition has never been evaluated in a patient with ascites. A patient with pancreatic cancer and malignant ascites was treated with dFdC 1,500 mg/m2 over 150 minutes weekly for 3 weeks, repeated every 4 weeks. Serial plasma and ascites samples were obtained on weeks 1 and 2 of cycle 2. High-pressure liquid chromatography was used to quantify dFdC and dFdU in plasma and ascites. The systemic dispositions of dFdC and dFdU were similar to those reported in patients without ascites. The concentration of dFdC in ascites approached 1 mg/ml. Ascitic fluid did not serve as a depot for dFdC, and the agent's concentration in ascites approached that at which its phosphorylation is saturated.
Delauter
B J
BJ
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pennsylvania, USA.
Ramanathan
R K
RK
Egorin
M J
MJ
Stover
L L
LL
Zuhowski
E G
EG
Plunkett
W
W
Zamboni
W C
WC
D015746:Abdominal Pain / Q000209:etiology; D000230:Adenocarcinoma / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy; D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001201:Ascites / Q000209:etiology* / Q000628:therapy*; D002408:Catheters, Indwelling; D002851:Chromatography, High Pressure Liquid; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000532:radiotherapy; D014552:Urinary Tract Infections / Q000209:etiology; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003841:Deoxycytidine; D005472:Fluorouracil; C084565:2',2'-difluoro-2'-deoxyuridine; D000093542:Gemcitabine