Bioavailability of paracetamol after oral administration to healthy volunteers. Influence of caffeine on rate and extent of absorption.

The absorption rate and the bioavailability of two commercially available paracetamol tablets were investigated in a panel of seven volunteers; one of these tablets contained a combination of 50 mg caffeine and paracetamol. Considering the urinary excretion data, it is concluded that the tablets release their contents completely; the absolute bioavailability, however, calculated from plasma concentrations, is lower than 100%, indicating a first-pass effect. A marked interindividual variation in first-pass effect was noticed. No general influence of caffeine on the extent of absorption of paracetamol could be established; there is, however, a slightly positive influence of caffeine on the absorption rate of paracetamol in six out of seven volunteers. It was concluded that this positive influence on absorption rate is not responsible for the established enhancement of paracetamol analgesia by caffeine.