CAFFEINE AS A METABOLIC PROBE - A COMPARISON OF THE METABOLIC RATIOS USED TO ASSESS CYP1A2 ACTIVITY

1 Caffeine is widely used as an in vivo probe for CYP1A2; the distribu tion/activity of this enzyme is reported to be reflected by metabolic ratios. 2 Several metabolic ratios using different combinations of uri nary metabolites have been used to measure CYP1A2, with varying conclu sions on its distribution. 3 A mathematical comparison of five metabol ic ratios claiming to reflect CYP1A2 activity was made using data from 237 healthy volunteers. 4 All five metabolic ratios were symmetricall y distributed. The five ratios however, measured at least three differ ent parameters, with no one ratio correlating exactly with any other. 5 Data in the literature claiming to measure CYP1A2 using caffeine may reflect other parameters. 6 The complex metabolism of caffeine togeth er with different parameters controlling the renal clearance of each m etabolite, makes the use of urinary metabolic ratios an inaccurate pro be for assessing the distribution of CYP1A2 activity in populations.