Linus Pauling Institute, College of Pharmacy, Oregon State University, 2900 SW Campus Way, Corvallis, Oregon 97331, United States.
UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States.
J Agric Food Chem. 2020 May 6;68(18):5212-5220. doi: 10.1021/acs.jafc.0c01077. Epub 2020 Apr 24.
Botanical dietary supplements produced from hops () containing the chemopreventive compound xanthohumol and phytoestrogen 8-prenylnaringenin are used by women to manage menopausal symptoms. Because of the long half-lives of prenylated hop phenols and reports that they inhibit certain cytochrome P450 enzymes, a botanically authenticated and chemically standardized hop extract was tested for Phase I pharmacokinetic drug interactions. Sixteen peri- and postmenopausal women consumed the hop extract twice daily for 2 weeks, and the pharmacokinetics of tolbutamide, caffeine, dextromethorphan, and alprazolam were evaluated before and after supplementation as probe substrates for the enzymes CYP2C9, CYP1A2, CYP2D6, and CYP3A4/5, respectively. The observed area under the time-concentration curves were unaffected, except for alprazolam which decreased 7.6% (564.6 ± 46.1 h·μg/L pre-hop and 521.9 ± 36.1 h·μg/L post-hop; -value 0.047), suggesting minor induction of CYP3A4/5. No enzyme inhibition was detected. According to FDA guidelines, this hop dietary supplement caused no clinically relevant pharmacokinetic interactions with respect to CYP2C9, CYP1A2, CYP2D6, or CYP3A4/5. The serum obtained after consumption of the hop extract was analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry to confirm compliance. Abundant Phase II conjugates of the hop prenylated phenols were observed including monoglucuronides and monosulfates as well as previously unreported diglucuronides and sulfate-glucuronic acid diconjugates.
植物性膳食补充剂由啤酒花（）制成，其中含有具有化学预防作用的化合物黄腐酚和植物雌激素 8-异戊烯基柚皮素，女性使用这些膳食补充剂来缓解更年期症状。由于具有长半衰期的丙烯基啤酒花酚和它们抑制某些细胞色素 P450 酶的报道，因此对经过植物学认证和化学标准化的啤酒花提取物进行了 I 期药代动力学药物相互作用测试。16 名绝经前后的女性每天两次服用该啤酒花提取物，持续 2 周，然后分别用甲苯磺丁脲、咖啡因、右美沙芬和阿普唑仑作为探针底物，评估补充前后这些酶 CYP2C9、CYP1A2、CYP2D6 和 CYP3A4/5 的药代动力学。除了阿普唑仑，观察到的时间-浓度曲线下面积没有变化，阿普唑仑减少了 7.6%（564.6 ± 46.1 h·μg/L 补充前和 521.9 ± 36.1 h·μg/L 补充后；-值 0.047），表明 CYP3A4/5 有轻微诱导。未检测到酶抑制。根据 FDA 指南，这种啤酒花膳食补充剂与 CYP2C9、CYP1A2、CYP2D6 或 CYP3A4/5 无临床相关的药代动力学相互作用。在服用啤酒花提取物后获得的血清使用超高效液相色谱-串联质谱法进行分析，以确认是否符合要求。观察到大量的啤酒花丙烯基酚的 II 期共轭物，包括单葡萄糖醛酸苷和单硫酸盐，以及以前未报道的双葡萄糖醛酸苷和硫酸盐-葡萄糖醛酸二共轭物。
