葡萄柚汁与药物相互作用的特征和个体差异

葡萄柚汁是一种柑桔类果汁 ,它能与近 4 0种药物在不同程度上发生相互作用。大多数受影响的药物口服生物利用度低、代谢过程受细胞色素P4 5 0 3A4 (CYP3A4 )的控制。有研究表明 ,葡萄柚汁能够抑制小肠CYP3A4介导的药物氧化代谢过程 ,导致血药浓度上升 ,从而使得药效增强或不良反应增加 ;葡萄柚汁与药物相互作用的个体差异与个体小肠CYP3A4的表达水平有关 ;呋喃香豆素类化合物是葡萄柚汁中关键的CYP3A4抑制剂

Grapefruit juice-drug interaction and individual variation

Grapefruit juice is a commonly consumed beverage. When administrated simultaneously, grapefruit juice can cause interaction at various degrees with around 40 drugs. The affected drugs vary greatly in therapeutical applications, such as calcium channel blockers, immunosuppressants, HMG CoA reductase inhibitors, HIV protease inhibitors, antihistamines, psychiatric medications, etc. In most cases, the affected drugs are substrates of a subtype of cytochrome P450 3A4(CYP3A4), and show quite low oral bioavailabilities. Thus, it is inferred that the interactions caused by grapefruit juice are due to the inhibition of intestinal CYP3A4. The magnitude of the interaction was highly variable interindividually but reproducible intraindividually. This is believed to be caused by the variation of intestinal CYP3A4 expression among individuals. Recent studies showed that some furanocoumarin derivatives in grapefruit juice are the causing components. And a sour orange juice containing furanocoumarins has shown clear interaction with felodipine similar to that of grapefruit juice. In general, the possible interaction with grapefruit juice should be awared of when using a drug that is lipophilic, selectively metabolized by CYP3A4, administrated at low dosage, and poor of oral bioavailability.