Fruit juice inhibition of uptake transport: a new type of food-drug interaction
Fruit juice inhibition of uptake transport: a new type of food-drug interaction
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DOI：
10.1111/j.1365-2125.2010.03722.x
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发表时间：
2010-11-01
影响因子：
3.4
通讯作者：
Bailey, David G.
中科院分区：
文献类型：
--
作者：
Bailey, David G.
本综述的重点是果汁通过抑制摄取转运来降低口服药物生物利用度的新型相互作用。这一发现基于与预期相反的结果，当时评估了柚子汁通过抑制肠道 MDR1 介导的外排转运来增加口服非索非那定在人体中的生物利用度的可能性。在后续研究中，与 MDR1 引起的外排底物转运相比，低浓度的葡萄柚或橙汁可能选择性地抑制体外 OATP1A2 介导的摄取。这些大量的果汁显着降低了口服非索非那定的生物利用度。葡萄柚是随后表征相互作用的代表性果汁。使用正常果汁量的体积效应关系研究使非索非那定的平均吸收量减半。个体差异和重现性数据表明临床相互作用涉及直接抑制肠道 OATP1A2。柚皮苷是主要的因果成分，表明水果和蔬菜中的其他黄酮类化合物也可能产生这种作用。果汁对非索非那定吸收的临床抑制持续时间超过 2 小时但少于 4 小时，表明通过果汁和药物消耗之间适当的时间间隔可以避免相互作用。葡萄柚汁降低了 OATP1A2 转运的几种药物（醋丁洛尔、塞利洛尔、非索非那定、他林洛尔、L-甲状腺素）的口服生物利用度，而橙汁对其他药物（阿替洛尔、塞利洛尔、环丙沙星、非索非那定）也有同样的作用。果汁对 OATP2B1 的临床抑制尚未解决，而 OATP1B1 的临床抑制似乎不太可能。葡萄柚汁和依托泊苷之间的相互作用似乎也相关。了解受影响的摄取转运蛋白和药物亲水性有助于预测与葡萄柚或橙汁的临床相互作用。
A new type of interaction in which fruit juices diminish oral drug bioavailability through inhibition of uptake transport is the focus of this review. The discovery was based on an opposite to anticipated finding when assessing the possibility of grapefruit juice increasing oral fexofenadine bioavailability in humans through inhibition of intestinal MDR1-mediated efflux transport. In follow-up investigations, grapefruit or orange juice at low concentrations potentially and selectively inhibited in vitro OATP1A2-mediated uptake compared with MDR1-caused efflux substrate transport. These juices at high volume dramatically depressed oral fexofenadine bioavailability. Grapefruit was the representative juice to characterize the interaction subsequently. A volume-effect relationship study using a normal juice amount halved average fexofenadine absorption. Individual variability and reproducibility data indicated the clinical interaction involved direct inhibition of intestinal OATP1A2. Naringin was a major causal component suggesting that other flavonoids in fruits and vegetables might also produce the effect. Duration of juice clinical inhibition of fexofenadine absorption lasted more than 2 h but less than 4 h indicating the interaction was avoidable with appropriate interval of time between juice and drug consumption. Grapefruit juice lowered the oral bioavailability of several medications transported by OATP1A2 (acebutolol, celiprolol, fexofenadine, talinolol, L-thyroxine) while orange juice did the same for others (atenolol, celiprolol, ciprofloxacin, fexofenadine). Juice clinical inhibition of OATP2B1 was unresolved while that of OATP1B1 seemed unlikely. The interaction between grapefruit juice and etoposide also seemed relevant. Knowledge of both affected uptake transporter and drug hydrophilicity assisted prediction of the clinical interaction with grapefruit or orange juice.