Total parenteral nutrition alters hepatic drug conjugation in rats

Total parenteral nutrition (TPN) provides complete nutritional support in settings in which patients cannot eat. TPN, typically administered through a central vein as an elemental nutrient solution, bypasses the intestinal tract and causes adverse effects to the gut and liver. TPN has also been shown to depress hepatic drug oxidation, but its effects on drug conjugation have not been characterized. The purpose of this research was to examine the effects of TPN on hepatic drug conjugation in male Sprague Dawley rats and to investigate the role of such factors as the composition of TPN solutions and the route of administration in contributing to alterations in hepatic drug metabolism. Results confirm that TPN depresses hepatic drug oxidation and further indicate that TPN diminishes the in vitro rate of hepatic conjugation reactions and decreases the total clearance of acetaminophen in vivo due to decreased formation of the sulfate metabolite. These changes occur independently of parenteral route of administration (portal vein vs. inferior vena cava) and may linger for greater than one week after normal feeding has been resumed. Substituting 25% of the nonprotein calories with lipid similarly alters drug metabolism. When the TPN solution is administered enterally, however, hepatic drug metabolism is unaffected compared to chow fed animals. These investigations suggest that intestinal physiology is an important regulator of hepatic drug metabolism.