Pharmacokinetics of gemcitabine and 2 ',2 '-difluorodeoxyuridine in a patient with ascites

Gemcitabine (dFdC) is a prodrug that undergoes metabolism by cytidine deami nase to form an inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU). The pharmacokinetics of dFdC and dFdU have been studied; however, their dispos ition has never been evaluated in a patient with ascites. A patient with pa ncreatic cancer and malignant ascites was treated with dFdC 1500 mg/m(2) ov er 150 minutes weekly for 3 weeks, repeated every 4 weeks. Serial plasma an d 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 asci tes. The systemic dispositions of dFdC and dFdU were similar to those repor ted in patients without ascites. The concentration of dFdC in ascites appro ached 1 mg/ml. Ascitic fluid did not serve as a depot for dFdC, and the age nt's concentration in ascites approached that at which its phosphorylation is saturated.