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 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 (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 CYP1A2 activity in vivo appears limited.

DOI: 10.1046/j.1365-2125.1999.00079.x

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