A pilot study of the effect of antipyrine on caffeine kinetics in six healthy volunteer subjects.

The potential interaction is described between caffeine and antipyrine, two drugs with a high probability of being concomitantly administered for the evaluation of liver metabolism. In order to determine the influence of antipyrine on the elimination of caffeine, salivary caffeine clearance was measured in six healthy volunteers prior to and 2 and 5 days after the administration of a single oral dose of 1000 mg of antipyrine. Total caffeine clearance increased on average by 24% (from 1.65 to 2.05 ml/min, P = 0.1) 2 days after antipyrine dosing, and 25% (from 1.65 to 2.06 ml/min, P < 0.01) 5 days after the administration of antipyrine, whereas the half-life decreased by around 24% (from 5.3 to 4 h, P = 0.09) after 2 days and 26% (from 5.3 to 3.9 h, P = 0.05) after 5 days. The apparent volume of distribution did not change. These results suggest that antipyrine is able to increase the elimination of caffeine, probably by means of inducing its hepatic metabolism. When both drugs are used sequentially in the same patient to assess the drug metabolizing activity of the liver, the caffeine test should be performed first.