Metabolism of drugs and carcinogens in man: antipyrine elimination as an indicator.
The suitability of the most commonly used "prototype" drug, viz, antipyrine, in predicting drug and carcinogen metabolism was evaluated, by studying in vivo antipyrine elimination rate (Ke) and in vitro metabolism of drugs and carcinogens in liver preparations in the same individuals. Our subjects were 20 adult males undergoing abdominal surgery for gastrojejunostomy, although antipyrine Ke could be studied in only 16 subjects. Correlations of the various in vito--in vivo parameters were positive between the parameter pairs: in vivo antipyrine Ke--in vitro benzopyrene hydroxylase; benzopyrene hydroxylase--aniline hydroxylase; and benzopyrene hydroxylase--gamma-glutamyl transferase. Aminopyrine demethylase did not correlate with any of the parameters studied. The degree of correlation between antipyrine Ke and benzopyrene hydroxylase was statistically significant but was not satisfactory for predictive purposes. Our study indicates some of the problems and limitations of in vivo--in vitro comparisons and confirms earlier doubts on the usefulness of antipyrine as a "prototype" drug for predicting drug and carcinogen metabolism in man.
D000328:Adult; D000368:Aged; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000378:metabolism; D000983:Antipyrine / Q000378:metabolism*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D002273:Carcinogens; D004364:Pharmaceutical Preparations; D000815:Aniline Hydroxylase; D001579:Benzopyrene Hydroxylase; D000633:Aminopyrine N-Demethylase; D005723:gamma-Glutamyltransferase; D000983:Antipyrine