Krishnaswamy K, Kalamegham R, Naidu N A
Br J Clin Pharmacol. 1984 Feb;17(2):139-46. doi: 10.1111/j.1365-2125.1984.tb02328.x.
The possible dietary influences on in vivo antipyrine and aminopyrine kinetics with reference to energy (1500, 1800, 3000 kcal) and protein (5, 10, 15, 20% protein energy-PE) intake were studied in a carefully controlled metabolic experiment in young healthy adult male volunteers aged between 25-34 years. Antipyrine and aminopyrine were used to evaluate drug metabolism. On 1500 kcal intake with 10% PE, the metabolism of both aminopyrine and antipyrine were significantly reduced whereas on 1800 kcal with 10% PE intake, only aminopyrine metabolism decreased significantly as compared to 3000 kcal with 10% PE. Antipyrine clearance on 1800 kcal with 10% PE however had not decreased to the same extent as on 1500 kcal with 10% PE. The results indicate that on low calorie intake with 10% PE, the drug metabolism is decreased. When the protein intake on 1500 kcal was doubled (20% PE) there was a significant stimulation of both aminopyrine and antipyrine metabolism. Aminopyrine and antipyrine clearances on 3000 kcal with 5% PE were significantly reduced as compared to 3000 kcal with 10% and 15% PE indicating that unlike proteins, carbohydrate and/or fat calories per se do not significantly stimulate drug metabolism. When the protein energy in the diet was increased from 5% to 10% or 15% at 3000 kcal, there was a stimulation of both antipyrine and aminopyrine metabolism. Significant differences between 10% and 15% of protein energy were not observed when the energy was adequate (3000 kcal). Therefore it is necessary to consider both proteins and energy as important variables affecting drug clearances from plasma in malnourished conditions.
在一项精心控制的代谢实验中,对年龄在25至34岁之间的年轻健康成年男性志愿者,研究了能量(1500、1800、3000千卡)和蛋白质(5%、10%、15%、20%蛋白质能量-PE)摄入量对体内安替比林和氨基比林动力学的可能饮食影响。使用安替比林和氨基比林来评估药物代谢。摄入1500千卡且蛋白质能量为10%时,氨基比林和安替比林的代谢均显著降低;而摄入1800千卡且蛋白质能量为10%时,与摄入3000千卡且蛋白质能量为10%相比,仅氨基比林代谢显著下降。然而,摄入1800千卡且蛋白质能量为10%时的安替比林清除率并未降至与摄入1500千卡且蛋白质能量为10%时相同的程度。结果表明,摄入低热量且蛋白质能量为10%时,药物代谢会降低。当1500千卡的蛋白质摄入量翻倍(20%蛋白质能量)时,氨基比林和安替比林的代谢均受到显著刺激。与摄入3000千卡且蛋白质能量为10%和15%相比,摄入3000千卡且蛋白质能量为5%时的氨基比林和安替比林清除率显著降低,这表明与蛋白质不同,碳水化合物和/或脂肪热量本身并不会显著刺激药物代谢。当饮食中的蛋白质能量在3000千卡时从5%增加到10%或15%时,安替比林和氨基比林的代谢均受到刺激。当能量充足(3000千卡)时,未观察到蛋白质能量为10%和15%之间的显著差异。因此,在营养不良的情况下,有必要将蛋白质和能量都视为影响药物从血浆中清除的重要变量。