Hydrolysis kinetics of ibuprofen piconol to ibuprofen were determined in vitro in plasma, whole blood, and serum. Varying initial concentrations of ibuprofen piconol with different anticoagulants (EDTA, heparin, citrate, or no anticoagulant) were used in determining the effects each had on the rate of ibuprofen piconol hydrolysis. Varying the initial concentration of ibuprofen piconol did not alter the hydrolysis half-life (concentration range from 50 to 200 micrograms/mL). The anticoagulant used altered the hydrolysis half-life. For plasma, the half-life was shortest when no anticoagulant was present (t 1/2 = 2.5 h) and longer with the presence of anticoagulants; for citrate, t 1/2 = 8.0 h, for heparin; t 1/2 = 15.5 h; and for EDTA, t 1/2 = 161.8 h. Red blood cell uptake of ibuprofen piconol was minimal and ranged from 0.4 to 4.1% over the ibuprofen piconol concentrations used in the study.