The primary objective of this four-way crossover study was to compare the concentration-time profile of paracetamol from a new rapidly absorbed paracetamol tablet containing sodium bicarbonate (PS) with a conventional paracetamol tablet (P), in a panel of 28 fed and fasted healthy volunteers. The results demonstrated that paracetamol was absorbed more rapidly from tablets containing sodium bicarbonate compared to conventional tablets, as indicated by a shorter tmax in both the fed and fasted state and a higher Cmax in the fasted state. The two formulations were bioequivalent with respect to area under curve (AUC). Food did not affect the extent of absorption from either formulation, as indicated by AUC, however, food did reduce the rate of absorption from both formulations, as indicated by a longer tmax and a lower Cmax. Metabolic activation of paracetamol to its oxidation metabolites, as assessed by combined partial clearances to subsequent secondary metabolites cysteine and mercapturic acid conjugates, indicated that the two formulations were bioequivalent in this respect.