Fuhr U
Institute for Pharmacology, Universität zu Köln, Germany.
Drug Saf. 1998 Apr;18(4):251-72. doi: 10.2165/00002018-199818040-00002.
Concomitant intake with grapefruit juice increases the concentrations of many drugs in humans. The effect seems to be mediated mainly by suppression of the cytochrome P450 enzyme CYP3A4 in the small intestine wall. This results in a diminished first pass metabolism with higher bioavailability and increased maximal plasma concentrations of substrates of this enzyme. The effect was most pronounced in drugs with a high first pass degradation and in many cases has the clear potential to reach clinical relevance, as shown by an occasional change in drug effects or tolerability. For felodipine, nitrendipine, nisoldipine and saquinavir, the interaction was most marked with median increases of area under the curve (AUC) and/or the maximum (peak) plasma drug concentration after single-dose administration (Cmax) values exceeding 70% of respective control periods. Less pronounced, but possibly relevant, concentration increases were found for nifedipine, nimodipine, verapamil, cyclosporin, midazolam, triazolam and terfenadine. This list is not complete because many drugs have not been studied yet. The components of grapefruit juice which are the most probable causes of the interactions are psoralen derivatives, but the flavonoid naringenin may also contribute. Concomitant grapefruit juice intake does not generally decrease the variability of drug pharmacokinetic parameters. Therefore, it is recommended that patients refrain from drinking grapefruit juice when they are taking a drug that is extensively metabolised, unless a lack of interaction has already been demonstrated for the drug. It is also recommended that drugs possibly interacting with grapefruit juice should be appropriately labelled. A place for grapefruit juice as a drug-sparing agent in treatment involving expensive medicine cannot be derived from the information currently available on grapefruit juice interactions.
与葡萄柚汁同时摄入会增加人体中许多药物的浓度。这种效应似乎主要是由小肠壁细胞色素P450酶CYP3A4的抑制介导的。这导致首过代谢减弱，生物利用度更高，且该酶底物的最大血浆浓度增加。这种效应在首过降解率高的药物中最为明显，在许多情况下显然有可能具有临床相关性，偶尔出现的药物效应或耐受性变化就表明了这一点。对于非洛地平、尼群地平、尼索地平以及沙奎那韦，单剂量给药后曲线下面积（AUC）和/或最大（峰）血浆药物浓度（Cmax）值的中位数增加超过各自对照期的70%，相互作用最为显著。对于硝苯地平、尼莫地平、维拉帕米、环孢素、咪达唑仑、三唑仑和特非那定，虽然浓度增加不太明显，但可能具有相关性。这份清单并不完整，因为许多药物尚未进行研究。葡萄柚汁中最可能导致相互作用的成分是补骨脂素衍生物，但黄酮类化合物柚皮苷也可能起作用。同时摄入葡萄柚汁一般不会降低药物药代动力学参数的变异性。因此，建议患者在服用广泛代谢的药物时不要饮用葡萄柚汁，除非已证明该药物不存在相互作用。还建议可能与葡萄柚汁相互作用的药物应进行适当标注。从目前关于葡萄柚汁相互作用的信息中无法得出葡萄柚汁在涉及昂贵药物的治疗中作为药物节省剂的作用。
