Raftogianis R B, Franklin M R, Galinsky R E
Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, University of Utah, Salt Lake City 84112, USA.
JPEN J Parenter Enteral Nutr. 1995 Jul-Aug;19(4):303-9. doi: 10.1177/0148607195019004303.
Total parenteral nutrition provides nutrition support in patients who are unable to eat. Long-term parenteral nutrition is accompanied by alterations in gut and liver function including changes in drug metabolism. This study examined the effects of lipid-free total parenteral nutrition in rats on (1) the overall elimination pharmacokinetics of acetaminophen, (2) changes in sulfation and glucuronidation pathways during acetaminophen elimination, and (3) hepatic drug metabolizing enzyme activities determined in vitro.
Chronic indwelling catheters were implanted in the aorta, inferior vena cava, and portal vein of adult male Sprague-Dawley rats. Total parenteral nutrition, consisting of 25% dextrose, 5% amino acids, electrolytes, and vitamins, was infused via the portal vein for up to 14 days. Acetaminophen pharmacokinetics were characterized in vivo and selected drug metabolizing enzyme activities were determined in vitro.
Parenteral nutrition for 10 days decreased the total clearance of acetaminophen by 23% (from 11.5 +/- 1.4 to 8.9 +/- 1.4 mL/min per kg; p < .05) and decreased the formation clearance to acetaminophen sulfate (from 6.2 +/- 0.4 to 3.9 +/- 0.5 mL/min per kg; p < .05). Parenteral nutrition decreased microsomal cytochrome P450 concentration (47%), p-nitroanisole demethylase activity (68%) and p-nitrophenol UDP-glucuronosyltransferase activity (58%). Cytosolic glutathione-S-transferase activity towards 1-chloro-2,4-dinitrobenzene decreased 29%. Sulfotransferase activity towards p-nitrophenol and acetaminophen was decreased 48% and 25%, respectively.
Lipid-free, total parenteral nutrition depresses drug conjugative metabolism in rats. The magnitude of this effect in humans remains to be investigated.
全胃肠外营养为无法进食的患者提供营养支持。长期胃肠外营养会伴随着肠道和肝脏功能的改变，包括药物代谢的变化。本研究检测了无脂全胃肠外营养对大鼠的影响：（1）对乙酰氨基酚的总体消除药代动力学；（2）对乙酰氨基酚消除过程中硫酸化和葡萄糖醛酸化途径的变化；（3）体外测定的肝脏药物代谢酶活性。
将慢性留置导管植入成年雄性Sprague-Dawley大鼠的主动脉、下腔静脉和门静脉。通过门静脉输注由25%葡萄糖、5%氨基酸、电解质和维生素组成的全胃肠外营养，持续长达14天。在体内表征对乙酰氨基酚的药代动力学，并在体外测定选定的药物代谢酶活性。
胃肠外营养10天使对乙酰氨基酚的总清除率降低了23%（从每千克11.5±1.4降至8.9±1.4 mL/min；p<.05），并使对乙酰氨基酚硫酸盐的生成清除率降低（从每千克6.2±0.4降至3.9±0.5 mL/min；p<.05）。胃肠外营养降低了微粒体细胞色素P450浓度（47%）、对硝基苯甲醚脱甲基酶活性（68%）和对硝基苯酚UDP-葡萄糖醛酸基转移酶活性（58%）。胞质谷胱甘肽-S-转移酶对1-氯-2,4-二硝基苯的活性降低了29%。磺基转移酶对对硝基苯酚和对乙酰氨基酚的活性分别降低了48%和25%。
无脂全胃肠外营养会抑制大鼠的药物结合代谢。这种效应在人类中的程度仍有待研究。
