Investigation of the pharmacokinetics of gemcitabine and 2 ',2 '-difluorodeoxyuridine in human plasma by liquid chromatography

Genicitabine (2',2'-difluorodeoxycytidine, dFdC) is a difluorine-substituted deoxycytidine analogue that has demonstrated antitumor activity against solid tumors. The pharmacokinetics of dFdC and its metabolite, 2',2'-difluorodeoxyuridine (dFdU) have been studied; however, their disposition has never been evaluated in a patient with bladder cancer. A patient with bladder cancer was treated with dFdC 1000mg/m(2) over a 30min period. The patient received a dFdC infusion once per week for 3 weeks followed by a rest week. Serial plasma samples were obtained prior to, during, and after completion of the infusion for determination of dFdC and dFdU concentrations. dFdC and dFdU concentrations were measured using normal-phase high-performance liquid chromatography and one-compartment open model methods. Maximum plasma concentrations (C-max) and area under the plasma concentration-time curve for dFdC and dFdU were 24.5 mug/ml and 11200 mug/Lh, 4.9.1 mug/ml and 272,800 mug/Lh, respectively. (C) 2004 Elsevier Inc. All rights reserved.