A New Rapidly Absorbed Paracetamol Tablet Containing Sodium Bicarbonate. I. A Four-Way Crossover Study to Compare the Concentration–Time Profile of Paracetamol from the New Paracetamol/Sodium Bicarbonate Tablet and a Conventional Paracetamol Tablet in Fed and Fasted Volunteers

ABSTRACT

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 t_max in both the fed and fasted state and a higher C_max 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 t_max and a lower C_max. 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.

• Bioequivalence
• Metabolism
• Paracetamol
• Rate of absorption