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Pharmacokinetics of Gemcitabine and 2′,2′‐Difluorodeoxyuridine in a Patient with Ascites
Author(s) -
Delauter Brian J.,
Ramanathan Ramesh K.,
Egorin Merrill J.,
Stover Lori L.,
Zuhowski Eleanor G.,
Plunkett William,
Zamboni William C.
Publication year - 2000
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.20.15.1204.34586
Subject(s) - ascites , pharmacokinetics , gemcitabine , prodrug , metabolite , cytidine deaminase , chemistry , pharmacology , medicine , endocrinology , chemotherapy , biology , biochemistry , enzyme
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 1500 mg/m 2 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.