Brexpiprazole (BRX) is approved for the treatment of schizophrenia and major depressive disorders and it is mainly metabolized by CYP3A4 and CYP2D6. Grapefruit juice (GFJ), pomegranate juice (PJ) and tomato juice (TJ) have the potential to inhibit CYP3A4 enzymes in the body. However, fruit juice–drug interactions between BRX and GFJ, PJ and TJ have not been studied extensively. The present study describes the influence of GFJ, PJ and TJ on the pharmacokinetic parameters of BRX in rats. The study samples were analyzed using a mass-accurate and single-step bioanalytical method by ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry over a wide calibration range of 20–1,500 ng/ml. The results of the pharmacokinetic study denoted that the combined administration of GFJ and PJ could increase systemic exposure of BRX. The area under the curve of BRX increased 3.43- and 1.88-fold with co-administration of GFJ and PJ, respectively, while TJ with BRX had no effect on the area under the curve. Time to peak concentration and half-life were not significantly changed by any juice co-administration. The results show that GFJ and PJ affect the pharmacokinetic profile of BRX and hence advice needs to be given to patients.

中文翻译：

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UHPLC-QTOF-MS研究葡萄柚汁、石榴汁和番茄汁对布立哌唑大鼠体内药代动力学的影响

Brexpiprazole (BRX) 被批准用于治疗精神分裂症和重度抑郁症，主要通过 CYP3A4 和 CYP2D6 代谢。葡萄柚汁 (GFJ)、石榴汁 (PJ) 和番茄汁 (TJ) 具有抑制体内 CYP3A4 酶的潜力。然而，BRX 和 GFJ、PJ 和 TJ 之间的果汁-药物相互作用尚未得到广泛研究。本研究描述了 GFJ、PJ 和 TJ 对大鼠 BRX 药代动力学参数的影响。通过超高效液相色谱-四极杆飞行时间质谱在 20-1,500 ng/ml 的宽校准范围内，使用质量准确和单步生物分析方法对研究样品进行了分析。药代动力学研究结果表明，GFJ 和 PJ 联合给药可增加 BRX 的全身暴露。BRX 曲线下面积与 GFJ 和 PJ 共同给药分别增加了 3.43 和 1.88 倍，而 TJ 与 BRX 对曲线下面积没有影响。任何果汁的共同给药都没有显着改变达到峰值浓度的时间和半衰期。结果表明 GFJ 和 PJ 会影响 BRX 的药代动力学特征，因此需要向患者提供建议。