This project has been terminated because of the lack of suitable test substrates. Literature searches revealed that the rate of metabolism of caffeine is significantly affected by caffeine ingestion, smoking and other substances that induce P450IA2 isozymes (e.g. char broiled beef). The variation in rates of caffeine metabolism in non-smoking volunteers encompasses the range of metabolism rates determined in smokers. Caffeine is not a good substrate for the determination of baseline rates of liver function as its rate of metabolism is too variable. A systematic search of the literature for compounds that may be demethylated by the P450IIE isozymes (i.e. induced by ethanol) revealed none suitable for human use; considered test compounds were found to be either carcinogenic or toxic.
