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

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-alpha) 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-alpha) 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-alpha) (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.