葡萄柚汁与药物的相互作用

THE INTERACTIONS BETWEEN GRAPEFRUIT JUICE AND DRUGS

饮食中的烟、酒、茶对药物的影响报道较多,但有关饮料与药物的相互作用国内尚未见报道,国外临床上已经观察到饮料与药物的相互作用可影响药物疗效并诱发药物不良反应。本文就国外近年来报道较多的葡萄柚汁与药物的相互作用加以综述。在研究酒精与非洛地平的相互作用中偶然发现用于掩盖酒精味道的葡萄柚汁能明显增加非洛地平的口服生物利用度,随后的研究证明葡萄柚汁通过选择性抑制细胞色素P4503A4(CYP3A4)在肠壁的表达进而抑制非洛地平的首过效应而起作用。葡萄柚汁的作用可维持24h,多次给予葡萄柚汁可导致非洛地平AUC和Cmax 的积累增加。个体间相互作用的差异与肠CYP3A4酶的蛋白表达有关,如具有较高CYP3A4水平的个体,其相互作用较大,即非洛地平的AUC和Cmax 增加较多。到目前为止,至少已研究了20种药物与葡萄柚汁之间的相互作用。具有被CYP3A4催化首过效应而致低生物利用度的药物与葡萄柚汁间有明显的相互作用,临床上常见的有:双氢吡啶类、特非那定、沙喹那韦、环孢素、咪达唑仑、三唑仑和维拉帕米等,也见于洛伐他汀(美降之)、西沙必利和阿司咪唑(息斯敏)。葡萄柚汁与药物相互作用的程度与不同个体的敏感性、饮用的葡萄柚汁种类和品种以及与服药有关的因素的影响有关。

There are many reports about the interactions between grapefruit juice (GJ) and drugs. The finding that GJ can markedly increase oral drug bioavailability was based on an unexpected observation from an interaction study between the felodipine and ethanol, in which GJ was used to mask the taste of ethanol. Subsequent investigations showed that GJ acted by reducing presystemic felodipine metabolism through selective inhibition cytochrome P4503A4 expression in the intestinal wall. The duration of effect of GJ can last 24 h, repeated GJ consumption can result in a cumulative increase in felodipine AUC and Cmax. The high variability of the magnitude of effect among individuals appeared dependent upon inherent differences in enteric CYP3A4 protein expression such that individuals with highest baseline CYP3A4 had the highest proportional increase. At least 20 other drugs have been assessed for an interaction with GJ. Medications with low oral bioavailability because of substantial presystemic metabolism mediated by CYP3A4 appear affected by GJ. Clinically relevant interactions seem likely for most dihydropyridines, terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may also occur with lovastatin, cisapride and astemizole. The importance of the interaction appears to be influenced by individual patient susceptibility, type and amount of GJ and administration-related factors. Although in vitro findings support the flavonoid, naringin, or the furanocoumarin, 6',7'-dihydroxybergamottin, as being active ingredients, a final decision on their importance to the interaction must await results from in vivo testing in humans.