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      Effects of tomato juice on the pharmacokinetics of CYP3A4-substrate drugs

      Atsuko Ohkubo;Tomomi Chida;Hidetomo Kikuchi;Tadashi Tsuda;Katsuyoshi Sunaga;Laboratory of Pharmacotherapy, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University;  
      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.
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