Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman 11196, Jordan.
Herbresearch Germany, 86874 Mattsies, Germany.
Molecules. 2023 Feb 24;28(5):2117. doi: 10.3390/molecules28052117.
The L. (pomegranate) fruit juice contains large amounts of polyphenols, mainly tannins such as ellagitannin, punicalagin, and punicalin, and flavonoids such as anthocyanins, flavan-3-ols, and flavonols. These constituents have high antioxidant, anti-inflammatory, anti-diabetic, anti-obesity, and anticancer activities. Because of these activities, many patients may consume pomegranate juice (PJ) with or without their doctor's knowledge. This may raise any significant medication errors or benefits because of food-drug interactions that modulate the drug's pharmacokinetics or pharmacodynamics. It has been shown that some drugs exhibited no interaction with pomegranate, such as theophylline. On the other hand, observational studies reported that PJ prolonged the pharmacodynamics of warfarin and sildenafil. Furthermore, since it has been shown that pomegranate constituents inhibit cytochrome P450 (CYP450) activities such as CYP3A4 and CYP2C9, PJ may affect intestinal and liver metabolism of CYP3A4 and CYP2C9-mediated drugs. This review summarizes the preclinical and clinical studies that investigated the impact of oral PJ administration on the pharmacokinetics of drugs that are metabolized by CYP3A4 and CYP2C9. Thus, it will serve as a future road map for researchers and policymakers in the fields of drug-herb, drug-food and drug-beverage interactions. Preclinical studies revealed that prolonged administration of PJ increased the absorption, and therefore the bioavailability, of buspirone, nitrendipine, metronidazole, saquinavir, and sildenafil via reducing the intestinal CYP3A4 and CYP2C9. On the other hand, clinical studies are limited to a single dose of PJ administration that needs to be protocoled with prolonged administration to observe a significant interaction.
石榴汁含有大量的多酚类物质，主要有单宁类（如鞣花单宁、安石榴甙和安石榴酸）、类黄酮（如花青素、黄烷-3-醇和黄酮醇）。这些成分具有很强的抗氧化、抗炎、抗糖尿病、抗肥胖和抗癌活性。由于这些活性，许多患者可能在未经医生允许的情况下饮用石榴汁（PJ）。这可能会导致因食物-药物相互作用而产生药物药代动力学或药效学的显著变化，从而导致药物相互作用或益处。有研究表明，某些药物与石榴没有相互作用，如茶碱。另一方面，观察性研究报道 PJ 延长了华法林和西地那非的药效学。此外，由于已经表明石榴的成分抑制细胞色素 P450（CYP450）的活性，如 CYP3A4 和 CYP2C9，PJ 可能会影响 CYP3A4 和 CYP2C9 介导的药物的肠道和肝脏代谢。本综述总结了研究口服 PJ 给药对 CYP3A4 和 CYP2C9 代谢的药物药代动力学影响的临床前和临床研究。因此，它将为药物-草药、药物-食物和药物-饮料相互作用领域的研究人员和政策制定者提供未来的路线图。临床前研究表明，PJ 的长期给药通过减少肠道 CYP3A4 和 CYP2C9，增加了丁螺环酮、尼群地平、甲硝唑、沙奎那韦和西地那非的吸收，从而提高了它们的生物利用度。另一方面，临床研究仅限于 PJ 的单次给药，需要进行长期给药方案以观察到显著的相互作用。
