Ohkubo Atsuko, Chida Tomomi, Kikuchi Hidetomo, Tsuda Tadashi, Sunaga Katsuyoshi
Laboratory of Pharmacotherapy, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai 1-1, Sakado, Saitama 350-0295, Japan.
Asian J Pharm Sci. 2017 Sep;12(5):464-469. doi: 10.1016/j.ajps.2017.05.004. Epub 2017 May 12.
We previously demonstrated that tomato juice (TJ) contains potent mechanism-based inhibitor(s) of CYP3A4. In this study, we investigated the effects of TJ and grapefruit juice (GFJ) on the pharmacokinetics of the CYP3A4-substrate drugs, nifedipine (NFP) and midazolam (MDZ), in male Wistar rats. Oral administration of GFJ 90 min before the intraduodenal administration of NFP or MDZ increased the area under the concentration-time curves (AUCs) of NFP and MDZ by 32.4% and 89.4%, respectively. TJ increased MDZ blood concentrations and AUC after intraduodenal MDZ administration; however, it had no effect on NFP. When MDZ and NFP were intravenously administered, GFJ significantly increased the AUC of MDZ, but only slightly increased that of NFP. In contrast, TJ only slightly increased the AUC of MDZ. These results suggest that, similar to GFJ, TJ influences the pharmacokinetics of CYP3A4-substrate drugs; however, it may be a drug-dependent partial effect.
我们之前证明番茄汁（TJ）含有强效的基于机制的CYP3A4抑制剂。在本研究中，我们调查了TJ和葡萄柚汁（GFJ）对雄性Wistar大鼠体内CYP3A4底物药物硝苯地平（NFP）和咪达唑仑（MDZ）药代动力学的影响。在十二指肠内给予NFP或MDZ前90分钟口服GFJ，使NFP和MDZ的浓度-时间曲线下面积（AUC）分别增加了32.4%和89.4%。十二指肠内给予MDZ后，TJ增加了MDZ的血药浓度和AUC；然而，它对NFP没有影响。当静脉给予MDZ和NFP时，GFJ显著增加了MDZ的AUC，但仅略微增加了NFP的AUC。相比之下，TJ仅略微增加了MDZ的AUC。这些结果表明，与GFJ类似，TJ影响CYP3A4底物药物的药代动力学；然而，这可能是一种药物依赖性的部分效应。
