Tacrine is not an ideal probe drug for measuring CYP1A2 activity in vivo

Aims The aim of the present study was to examine the CYP1A2 substrate tacri ne as a possible alternative to caffeine for assessing CYP1A2 activity in v ivo. Methods Eighteen, healthy, nonsmoking men participated. Each volunteer was tested by caffeine (200 mg orally), and caffeine metabolic ratios were calc ulated. Subsequently, on two occasions, separated by at least 4 weeks, each volunteer was tested with tacrine (40 mg orally). The apparent oral cleara nce, partial clearances and different metabolic ratios of tacrine were dete rmined. Results The median oral clearances of tacrine in the two study periods were 1893 1h(-1) (range: 736-3098) and 1890 1 h(-1) (range: 438-4175), respecti vely. The interindividual coefficient of variation was 42% and 49%, respect ively. The intraindividual coefficients of variation ranged from 0.28% to 6 4% (median: 13%). In both study periods, the oral clearance of tacrine corr elated with the caffeine urinary metabolic ratio. However, only modest magn itudes of correlation were observed (r(s): 0.64-0.66, P < 0.01). No tacrine metabolic ratio correlating with the oral clearance of tacrine was found. Conclusion The applicability of tacrine as a probe drug for measuring CYP1A 2 activity in vivo appears limited.