Schmidt Lars E, Dalhoff Kim
Department of Clinical Pharmacology Q.7642, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Drugs. 2002;62(10):1481-502. doi: 10.2165/00003495-200262100-00005.
Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those associated with a high risk of treatment failure arising from a significantly reduced bioavailability in the fed state. Such interactions are frequently caused by chelation with components in food (as occurs with alendronic acid, clodronic acid, didanosine, etidronic acid, penicillamine and tetracycline) or dairy products (ciprofloxacin and norfloxacin), or by other direct interactions between the drug and certain food components (avitriptan, indinavir, itraconazole solution, levodopa, melphalan, mercaptopurine and perindopril). In addition, the physiological response to food intake, in particular gastric acid secretion, may reduce the bioavailability of certain drugs (ampicillin, azithromycin capsules, didanosine, erythromycin stearate or enteric coated, and isoniazid). For other drugs, concomitant food intake may result in an increase in drug bioavailability either because of a food-induced increase in drug solubility (albendazole, atovaquone, griseofulvin, isotretinoin, lovastatin, mefloquine, saquinavir and tacrolimus) or because of the secretion of gastric acid (itraconazole capsules) or bile (griseofulvin and halofantrine) in response to food intake. For most drugs, such an increase results in a desired increase in drug effect, but in others it may result in serious toxicity (halofantrine).
食物与药物之间的相互作用可能会无意中降低或增强药物疗效。大多数具有临床相关性的食物-药物相互作用是由食物引起的药物生物利用度变化所致。由于大多数药物的生物利用度与临床疗效相关,因此生物利用度是一个重要的药代动力学效应参数。然而,为了评估食物-药物相互作用的临床相关性,还必须量化食物摄入对药物临床疗效的影响。由于医疗保健系统中的质量审查,医疗服务提供者越来越需要制定识别和预防不良食物-药物相互作用的方法。在这篇原始文献综述中,我们试图提供具有临床相关性的食物-药物相互作用的药代动力学和临床疗效参数。最重要的相互作用是那些与进食状态下生物利用度显著降低导致治疗失败风险高相关的相互作用。此类相互作用通常是由与食物中的成分(如阿仑膦酸、氯膦酸、去羟肌苷、依替膦酸、青霉胺和四环素)或乳制品(环丙沙星和诺氟沙星)螯合,或由药物与某些食物成分之间的其他直接相互作用(阿伐曲坦、茚地那韦、伊曲康唑溶液、左旋多巴、美法仑、巯嘌呤和培哚普利)引起的。此外,对食物摄入的生理反应,特别是胃酸分泌,可能会降低某些药物的生物利用度(氨苄西林、阿奇霉素胶囊、去羟肌苷、硬脂酸红霉素或肠溶制剂,以及异烟肼)。对于其他药物,同时摄入食物可能会导致药物生物利用度增加,这要么是因为食物引起药物溶解度增加(阿苯达唑、阿托伐醌、灰黄霉素、异维A酸、洛伐他汀、甲氟喹、沙奎那韦和他克莫司),要么是因为进食后胃酸(伊曲康唑胶囊)或胆汁(灰黄霉素和卤泛群)分泌。对于大多数药物,这种增加会导致药物疗效的预期增加,但对于其他药物,可能会导致严重毒性(卤泛群)。