Effects of parenteral and enteral hyperalimentation on hepatic drug metabolism in the rat.

Whereas patients receiving parenteral hyperalimentation frequently have abnormalities in serum liver enzymes, the influence of i.v. administration of hypertonic glucose-protein solutions on hepatic function has received little attention. Recent data from this laboratory indicated that in vivo clearance of pentobarbital was significantly decreased in rats receiving total parenteral hyperalimentation (TPN) vs. animals receiving the same hyperalimentation solution enterally (total enteral hyperalimentation; TEN). To determine the cause of this decreased clearance, we have analyzed mixed-function oxidase activity in hepatic microsomes prepared from livers of rats receiving 7 day continuous i.v. or i.g. infusions of hypertonic glucose (25%) combined with fibrin hydrolysate or crystalline amino acids. Hepatic microsomal cytochrome P-450 and capacity for demethylation of meperidine and hydroxylation of pentobarbital were significantly reduced in TPN animals as compared to TEN and ad libitum chow-fed control rats. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of microsomal protein revealed increased staining of a 46,500 molecular weight band and decreased intensity of a 52,700 molecular weight band in TPN experiments as compared to TEN studies. Increasing amino acid concentration in infusions to 4.25% from the standard 2.75% resulted in marked reductions in hepatic microsomal drug metabolism in enterally hyperalimented animals. These studies show that the route of alimentation delivery has an important influence on hepatic drug metabolic function in rats and suggest that quantitative and/or qualitative differences in hepatic delivery of protein may be responsible for the quantitative and qualitative differences in hepatic microsomal mixed-function oxidases observed between TPN and TEN animals. If similar changes occur in humans receiving TPN, major alterations in drug regimens may be required.