Earl-Salotti G I, Charland S L
Department of Pharmacy Practice and Administration, Philadelphia College of Pharmacy and Science.
JPEN J Parenter Enteral Nutr. 1994 Sep-Oct;18(5):458-65. doi: 10.1177/0148607194018005458.
Total parenteral nutrition (TPN) has been shown to affect liver function tests. Additional investigations in animals and humans have demonstrated that hepatic cytochrome P-450 content and enzyme activity are also affected.
To review the literature on the effect of TPN on hepatic cytochrome P-450, an English-language literature search was performed using MEDLINE (1966 through 1993).
Studies in laboratory rats show that administration of dextrose, with or without amino acids, decreases the cytochrome P-450 content and the in vitro or in vivo microsomal oxidation rates of various drugs. The addition of lipid emulsions to TPN decreases oxidation rates for meperidine demethylase but does not affect ethoxyresorufin deethylase. Using immunoquantitation, it was shown that the components of TPN selectively affect specific hepatic P-450 enzymes. In humans, dextrose decreases antipyrine clearance, whereas amino acids and possibly lipids increase antipyrine clearance. However, the effects of protein-calorie malnutrition in these studies obscure the results.
Possible mechanisms for the reduction of hepatic cytochrome P-450 seen during TPN administration include altered gastrointestinal hormone response, mucosal barrier, and the effect of sepsis. Additional studies are needed to determine the actual mechanisms of hepatic cytochrome P-450 reduction observed during TPN.
全胃肠外营养（TPN）已被证明会影响肝功能检查。对动物和人类的进一步研究表明，肝细胞色素P - 450含量和酶活性也会受到影响。
为了回顾关于TPN对肝细胞色素P - 450影响的文献，使用MEDLINE（1966年至1993年）进行了英文文献检索。
对实验大鼠的研究表明，给予葡萄糖，无论有无氨基酸，都会降低细胞色素P - 450含量以及各种药物的体外或体内微粒体氧化速率。在TPN中添加脂肪乳剂会降低哌替啶脱甲基酶的氧化速率，但不影响乙氧异羟肟酸脱乙基酶。通过免疫定量分析表明，TPN的成分选择性地影响特定的肝P - 450酶。在人类中，葡萄糖会降低安替比林清除率，而氨基酸以及可能的脂肪会增加安替比林清除率。然而，这些研究中蛋白质 - 热量营养不良的影响使结果变得模糊。
TPN给药期间肝细胞色素P - 450减少的可能机制包括胃肠道激素反应改变、黏膜屏障以及脓毒症的影响。需要进一步研究以确定TPN期间观察到的肝细胞色素P - 450减少的实际机制。
