The Effect of Chronic Parenteral Carbohydrate Administration on Drug Metabolism in the Rat.

摘要

Dietary factors can affect the liver's ability to metabolize drugs; however, few studies have been done to show the effects of parenteral nutrition on drug metabolism. The effects of chronic parenteral carbohydrate administration on hepatic microsomal enzyme activity were studied in the rat. Daily intraperitoneal injections of both glucose and fructose resulted in a significantly decreased cytochrome P-450 content with subsequent losses in mixed function oxidase activity (ethylmorphine N-demethylation) by the fifth day. Aniline hydroxylation, however, was not significantly decreased until the seventh day, suggesting that the hepatic metabolism of ethylmorphine and aniline is mediated through different forms of cytochrome P-450. In vivo assessment using antipyrine half-lives confirmed this decrease in mixed function oxidase activity. The administration of carbohydrate produced fatty infiltration and glycogen depletion of the liver. This fatty infiltration was probably due to increased lipogenesis with decreased oxidative metabolism of fat by the liver, since all groups received the identical quantity of specific nutrients. The glycogen depletion may have been due to increased hepatic cyclic AMP. The decreased hepatic mixed function oxidase activity could have been the result of sustained hyperglycemia, hypoinsulinemia, and/or increased levels of hepatic cyclic AMP. (Author)