Larsen_1999_Br.J.Clin.Pharmacol_48_663

AIMS: The aim of the present study was to examine the CYP1A2 substrate tacrine as a possible alternative to caffeine for assessing CYP1A2 activity in vivo.
METHODS: Eighteen, healthy, nonsmoking men participated. Each volunteer was tested by caffeine (200 mg orally), and caffeine metabolic ratios were calculated. Subsequently, on two occasions, separated by at least 4 weeks, each volunteer was tested with tacrine (40 mg orally). The apparent oral clearance, partial clearances and different metabolic ratios of tacrine were determined.
RESULTS: The median oral clearances of tacrine in the two study periods were 1893 l h-1 (range: 736-3098) and 1890 l h-1 (range: 438-4175), respectively. The interindividual coefficient of variation was 42% and 49%, respectively. The intraindividual coefficients of variation ranged from 0.28% to 64% (median: 13%). In both study periods, the oral clearance of tacrine correlated with the caffeine urinary metabolic ratio. However, only modest magnitudes of correlation were observed (rs: 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 CYP1A2 activity in vivo appears limited.