1 The possible dietary influences on in vivo antipyrine and aminopyrine kinetics with reference to energy (1500, 1800, 3000 kcal) and protein (5, 10, 15, 20% protein energy-PE) intake were studied in a carefully controlled metabolic experiment in young healthy adult male volunteers aged between 25-34 years. 2 Antipyrine and aminopyrine were used to evaluate drug metabolism. 3 On 1500 kcal intake with 10% PE, the metabolism of both aminopyrine and antipyrine were significantly reduced whereas on 1800 kcal with 10% PE intake, only aminopyrine metabolism decreased significantly as compared to 3000 kcal with 10% PE. 4 Antipyrine clearance on 1800 kcal with 10% PE however had not decreased to the same extent as on 1500 kcal with 10% PE. The results indicate that on low calorie intake with 10% PE, the drug metabolism is decreased. 5 When the protein intake on 1500 kcal was doubled (20% PE) there was a significant stimulation of both aminopyrine and antipyrine metabolism. 6 Aminopyrine and antipyrine clearances on 3000 kcal with 5% PE were significantly reduced as compared to 3000 kcal with 10% and 15% PE indicating that unlike proteins, carbohydrate and/or fat calories per se do not significantly stimulate drug metabolism. 7 When the protein energy in the diet was increased from 5% to 10% or 15% at 3000 kcal, there was a stimulation of both antipyrine and aminopyrine metabolism. 8 Significant differences between 10% and 15% of protein energy were not observed when the energy was adequate (3000 kcal). 9 Therefore it is necessary to consider both proteins and energy as important variables affecting drug clearances from plasma in malnourished conditions.

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.

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