A rapid, sensitive and specific method to quantify diclofenac in human plasma using indomethacin as the internal standard (IS) is described. Samples were extracted using protein precipitation protocol and analyzed by high performance liquid chromatography coupled to ultraviolet detection at 276 nm. Chromatography was performed isocratically with a run time of 8.0 min and the retention time observed for diclofenac and IS was 6.0 and 7.0 min, respectively. The calibration curve was linear over the range 50-4,000 ng/ml; (r(2)>0.9995). The mean recovery of diclofenac ranged from 88.76 to 99.14% and the limit of quantification was 50 ng/ml. Intrabatch precision and accuracy (%CV) of the method ranged from 0.86 to 7.60%, and 99.34 to 103.8%, respectively. Interbatch precision (%CV) and accuracy ranged from 0.26 to 11.4%, and 92.00 to 105.34%, respectively. This H PLC method was used to determine the relative pharmacokinetics of two diclofenac-cholestyramine 140 mg capsule formulations. The study was conducted using all open, randomized and crossover design with a 1-week washout interval. A single 140 mg dose (equivalent to 70 mg of diclofenac) of each formulation was administered to 26 healthy volunteers (13 males and 13 females) and blood samples were obtained over 12-h interval. The geometric nican of diclofenac-cholestyramine/Flotac (R) ratio was 90.53% for AUC(0-12) and 100.22% for C(max). Since the 90% CI for C(max) and AUCs ratios were all inside the 80-125% interval, it was concluded that the diclofenac-cholestyramine test formulation is bioequivalent to Flotac (R) regarding both the rate and the extent of absorption.472132140