A pharmacokinetic study investigating the rate of absorption of a 500 mg dose of a rapidly absorbed paracetamol tablet and a standard paracetamol tablet

ABSTRACT

Objective: A rapidly absorbed tablet formulation of paracetamol containing sodium bicarbonate (PS) has been previously shown to be absorbed at least twice as fast as a standard paracetamol tablet (P) at a 1 g dose. In South America and Asia it is customary for patients to take a 500 mg dose of analgesic. The objective of this pharmacokinetic study was to compare the rate of absorption of PS versus P at a 500 mg dose.

Research design and methods: An open, randomized, single dose, cross-over study. Thirty Hispanic healthy volunteers randomly received a 500 mg dose taken orally with 50 mL of water 2 h after a standard breakfast. Blood samples were taken up to 10 h post-dose. Plasma concentrations of paracetamol were determined by HPLC with UV detection.

Main outcome measures: AUC_{0–30 min}, C_{plasma 30 min} and T_max were analyzed non-parametrically by the Wilcoxon's rank sum test. A linear mixed effects model was used to analyze the logarithmically transformed AUC_0–∝ and C_max. Bioequivalence was accepted if the 90% confidence intervals (CI) for the ratio of the means of the primary pharmacokinetic variable AUC_0–∝ lay completely within the range 0.80–1.25.

Results: AUC_{0–30 min} and C_{plasma 30 min} were significantly greater and T_max was significantly shorter (all p < 0.0001) for PS versus P. The formulations were bioequivalent for AUC_0–∝ (90% CI 0.99:1.05) and no statistical difference was seen for C_max (95% CI 0.91:1.14).

Conclusions: Paracetamol was absorbed at least twice as fast from PS compared to P at a 500 mg dose. The extent of absorption was equivalent for both formulations.

Key words: :

• Paracetamol
• Pharmacokinetic
• Rate of absorption
• Sodium bicarbonate