Interactions between grapefruit juice and cardiovascular drugs.
Interactions between grapefruit juice and cardiovascular drugs.
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DOI：
10.2165/00129784-200404050-00002
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发表时间：
2004-01-01
期刊：
影响因子：
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通讯作者：
Dresser, George K
中科院分区：
文献类型：
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作者：
Bailey, David G;Dresser, George K
葡萄柚汁可以通过不同的机制改变口服药物的药代动力学。肠道细胞色素P450 (CYP) 3A4的不可逆失活是由单个正常量的商业西柚汁（例如200-300毫升）或整个新鲜水果段引起的。因此，全身前代谢减少，口服药物的生物利用度增加。口服药物生物利用度可在饮用果汁24小时后提高。抑制p糖蛋白（P-gp）是通过减少肠道和/或肝脏外排转运来增加口服药物生物利用度的可能机制。最近，研究人员在体外观察了葡萄柚汁对有机阴离子转运多肽的抑制作用；肠道摄取转运随着口服药物生物利用度的降低而减少。许多用于预防或治疗冠状动脉疾病及其并发症的药物已经被观察到或预测与葡萄柚汁相互作用。当使用HMG-CoA还原酶抑制剂阿托伐他汀、洛伐他汀或辛伐他汀治疗血脂异常时，这种相互作用可能增加横纹肌溶解的风险。潜在的替代药物有普伐他汀、氟伐他汀或瑞舒伐他汀。当使用非洛地平、尼卡地平、硝苯地平、尼索地平或尼群地平等二氢吡啶类药物治疗高血压时，这种相互作用也可能导致血管过度扩张。另一种药物是氨氯地平。相反，血管紧张素II型1受体拮抗剂氯沙坦的治疗效果可能被葡萄柚汁降低。葡萄柚汁与降糖药瑞格列奈相互作用可引起低血糖，与食欲抑制剂西布曲明相互作用可引起血压和心率升高。在心绞痛患者中，服用葡萄柚汁可导致维拉帕米引起房室传导障碍或氯吡洛凝胶引起抗血小板活性减弱。葡萄柚汁可能会增加抗心律失常药物的毒性，如胺碘酮、奎尼丁、二丙酰胺或普罗帕酮，以及充血性心力衰竭药物卡维地醇。一些治疗外周或中枢血管疾病的药物也可能与葡萄柚汁发生相互作用。与西地那非、他达拉非或伐地那非相互作用治疗勃起功能障碍，可引起严重的全身血管舒张，特别是与硝酸盐合用时。治疗偏头痛的麦角胺和葡萄柚汁的相互作用可能导致坏疽或中风。在中风中，与尼莫地平相互作用可引起全身性低血压。如果一种药物通过CYP3A4的全身前代谢或P-gp的外排转运具有较低的固有口服生物利用度，并且可能产生严重的过量毒性，则在药物治疗期间完全避免葡萄柚汁似乎是强制性的。虽然药物反应的改变因人而异，但结果很难预测，避免联合用药将保证避免毒性。老年人的风险尤其大，因为他们经常服用处方药，而且经常喝葡萄柚汁。
Grapefruit juice can alter oral drug pharmacokinetics by different mechanisms. Irreversible inactivation of intestinal cytochrome P450 (CYP) 3A4 is produced by commercial grapefruit juice given as a single normal amount (e.g. 200-300 mL) or by whole fresh fruit segments. As a result, presystemic metabolism is reduced and oral drug bioavailability increased. Enhanced oral drug bioavailability can occur 24 hours after juice consumption. Inhibition of P-glycoprotein (P-gp) is a possible mechanism that increases oral drug bioavailability by reducing intestinal and/or hepatic efflux transport. Recently, inhibition of organic anion transporting polypeptides by grapefruit juice was observed in vitro; intestinal uptake transport appeared decreased as oral drug bioavailability was reduced. Numerous medications used in the prevention or treatment of coronary artery disease and its complications have been observed or are predicted to interact with grapefruit juice. Such interactions may increase the risk of rhabdomyolysis when dyslipidemia is treated with the HMG-CoA reductase inhibitors atorvastatin, lovastatin, or simvastatin. Potential alternative agents are pravastatin, fluvastatin, or rosuvastatin. Such interactions might also cause excessive vasodilatation when hypertension is managed with the dihydropyridines felodipine, nicardipine, nifedipine, nisoldipine, or nitrendipine. An alternative agent could be amlodipine. In contrast, the therapeutic effect of the angiotensin II type 1 receptor antagonist losartan may be reduced by grapefruit juice. Grapefruit juice interacting with the antidiabetic agent repaglinide may cause hypoglycemia, and interaction with the appetite suppressant sibutramine may cause elevated BP and HR. In angina pectoris, administration of grapefruit juice could result in atrioventricular conduction disorders with verapamil or attenuated antiplatelet activity with clopidrogel. Grapefruit juice may enhance drug toxicity for antiarrhythmic agents such as amiodarone, quinidine, disopyramide, or propafenone, and for the congestive heart failure drug, carvediol. Some drugs for the treatment of peripheral or central vascular disease also have the potential to interact with grapefruit juice. Interaction with sildenafil, tadalafil, or vardenafil for erectile dysfunction, may cause serious systemic vasodilatation especially when combined with a nitrate. Interaction between ergotamine for migraine and grapefruit juice may cause gangrene or stroke. In stroke, interaction with nimodipine may cause systemic hypotension. If a drug has low inherent oral bioavailability from presystemic metabolism by CYP3A4 or efflux transport by P-gp and the potential to produce serious overdose toxicity, avoidance of grapefruit juice entirely during pharmacotherapy appears mandatory. Although altered drug response is variable among individuals, the outcome is difficult to predict and avoiding the combination will guarantee toxicity is prevented. The elderly are at particular risk, as they are often prescribed medications and frequently consume grapefruit juice.