Burns J J, Conney A H
Proc R Soc Med. 1965 Nov;58(11 Part 2):955-60. doi: 10.1177/003591576505811P203.
Studies in recent years have disclosed two types of drug interaction which may be important in drug therapy:(1) Administration of one drug can speed up the metabolism of another drug. Animal experiments show that this results from the ability of drugs to induce the synthesis of drug-metabolizing enzymes in liver microsomes. This effect has considerable importance in pharmacologic and toxicologic studies carried out in animals, and recent work indicates that it may explain altered therapeutic responses observed in some patients when they receive several drugs at the same time. Substances present in the environment, such as the insecticides chlordane and DDT, have been shown in animals to stimulate drug-metabolizing enzymes in liver, but the significance of this observation for man is not known. Drugs which stimulate drug metabolism also enhance the hydroxylation of testosterone, estradiol, progesterone and cortisol by enzymes in liver microsomes. Further research is required to establish the physiological importance of this interaction of drugs in steroid metabolism.(2) One drug may inhibit the metabolism of another drug and thus intensify and prolong its pharmacologic action. Although this effect is well documented in animals, recent reports suggest that this may also be important in man. For instance, the action of coumarin anticoagulants can be potentiated by administration of certain drugs which inhibit their metabolism. Monoamine oxidase inhibitors block the metabolism of certain sympathomimetic amines and this can lead to serious side-effects. Thus, hypertensive crises have been observed in patients receiving monoamine oxidase inhibitors who have eaten cheese with a high tyramine content.
（1）一种药物的给药可加速另一种药物的代谢。动物实验表明，这是由于药物能够诱导肝微粒体中药物代谢酶的合成。这种效应在对动物进行的药理学和毒理学研究中具有相当重要的意义，并且最近的研究表明，这可能解释了一些患者同时服用几种药物时观察到的治疗反应改变。环境中存在的物质，如杀虫剂氯丹和滴滴涕，已在动物实验中显示可刺激肝脏中的药物代谢酶，但这一观察结果对人类的意义尚不清楚。刺激药物代谢的药物还会增强肝微粒体中酶对睾酮、雌二醇、孕酮和皮质醇的羟基化作用。需要进一步研究来确定药物在类固醇代谢中的这种相互作用的生理重要性。（2）一种药物可能会抑制另一种药物的代谢，从而增强并延长其药理作用。尽管这种效应在动物实验中有充分的记录，但最近的报告表明这在人类中也可能很重要。例如，香豆素类抗凝剂的作用可通过给予某些抑制其代谢的药物而增强。单胺氧化酶抑制剂会阻断某些拟交感神经胺的代谢，这可能导致严重的副作用。因此，在服用单胺氧化酶抑制剂的患者中，如果食用了富含酪胺的奶酪，就会观察到高血压危象。
