Walter-Sack I, Klotz U
Department of Medicine, University of Heidelberg, Germany.
Clin Pharmacokinet. 1996 Jul;31(1):47-64. doi: 10.2165/00003088-199631010-00004.
Genetic and environmental factors contribute to a wide inter- and intraindividual variability in drug metabolism. Among the environmental factors that may influence drug metabolism, the diet and nutritional status of the individuals are important determinants. As altered drug-metabolising enzyme activities can influence the intensity and duration of drug action, such factors should be considered in pharmacotherapy. For this reason the effects of dietary energy, protein deficiency, nutritional ingredients, special diet forms and nutrition regimens and malnutritional states must be differentiated. In various pharmacokinetic studies different model drugs metabolised either by oxidative phase I pathways [e.g. phenazone (antipyrine), aminopyrine, phenacetin, theophylline, propranolol, nifedipine] or phase II conjugation reactions [e.g. paracetamol (acetaminophen), oxazepam] were used and from the calculated pharmacokinetic data some information on the involved and affected drug-metabolising enzymes [e.g. cytochrome P450 (CYP) subspecies, glucuronosyltransferases] can be generated. It is well known that smoking, charcoal broiled food or cruciferous vegetables induce the metabolism of many xenobiotics, whereas grapefruit juice increases the oral bioavailability of the high clearance drugs nifedipine, nitrendipine or felodipine by inhibiting their presystemic (intestinal) elimination. Energy deficiency, and especially a low intake of protein, will cause a decrease of about 20 to 40% in phenazone and theophylline clearance and elimination of those drugs can be accelerated by a protein-rich diet. In the same way, protein deficiency induced by either vegetarian food or undernourishment will have the opposite pharmacokinetic consequences. On the basis of some more examples from the literature it is emphasised that the variable influence of the above factors should be taken into account in study participant selection and study design when the pharmacokinetics of a drug must be determined in healthy individuals and/or patients.
遗传和环境因素导致药物代谢在个体间和个体内存在广泛差异。在可能影响药物代谢的环境因素中，个体的饮食和营养状况是重要决定因素。由于药物代谢酶活性的改变会影响药物作用的强度和持续时间，因此在药物治疗中应考虑这些因素。因此，必须区分饮食能量、蛋白质缺乏、营养成分、特殊饮食形式和营养方案以及营养不良状态的影响。在各种药代动力学研究中，使用了不同的模型药物，这些药物通过氧化I相途径[如非那宗（安替比林）、氨基比林、非那西丁、茶碱、普萘洛尔、硝苯地平]或II相结合反应[如对乙酰氨基酚（扑热息痛）、奥沙西泮]进行代谢，从计算得到的药代动力学数据中，可以获得一些关于所涉及和受影响的药物代谢酶[如细胞色素P450（CYP）亚型、葡糖醛酸转移酶]的信息。众所周知，吸烟、炭烤食品或十字花科蔬菜会诱导许多外源性物质的代谢，而葡萄柚汁通过抑制硝苯地平、尼群地平或非洛地平等高清除率药物的首过（肠道）消除，增加其口服生物利用度。能量缺乏，尤其是蛋白质摄入量低，会导致非那宗和茶碱清除率降低约20%至40%，富含蛋白质的饮食可加速这些药物的消除。同样，素食或营养不良引起的蛋白质缺乏会产生相反的药代动力学后果。基于文献中的更多实例，强调在健康个体和/或患者中测定药物药代动力学时，在研究参与者选择和研究设计中应考虑上述因素的可变影响。
