Hepatic drug metabolism in iron-, magnesium- and potassium-deficient rats

It is now apparent that the rate of microsomal drug metabolism in experimental animals is subject to alteration by such dietary deficiencies as protein, vatamins, fats and minerals. The evidence, both published and unpublished, showing the effects of iron, magnesium, and potassium dificiencies on the hepatic metabolism of foreign compounds in rats is discussed. Iron deficiency has been shown to lead to a marked stimulation in hepatic metabolism, in vitro and in vivo, of both Type I (aminopyrine) and Type II (aniline) substrates. Magnesium-deficient rats have been shown to have markedly lower in vivo and in vitro rates of hepatic drug metabolism, but the monovalent intracellular mineral potassium had no apparent effect on the in vitro enzymatic conversion of foreign compounds. Hypokalemia has been shown to alter the in vivo disposition of aminopyrine and pentobarbital as evidenced by an increased plasma half-life of aminopyrine and a longer pentobarbital sleeping time in potassium-deficient animals. Large segments of the world's population are in less than satisfactory nutritional status with respect to iron, magnesium, potassium, copper, and zinc and the relevancy to man of the data discussed must be ascertained. The role of dietary minerals in nonhepatic microsomal drug metabolism is also not yet known.