Schubert W, Cullberg G, Edgar B, Hedner T
Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Maturitas. 1994 Dec;20(2-3):155-63. doi: 10.1016/0378-5122(94)90012-4.
In an open, randomized, cross-over study the concentrations of 17 beta-estradiol and estrone in serum were measured over 192 hours in 8 ovariectomized women after a single oral dose intake of 2 mg micronized 17 beta-estradiol. The subjects were studied with and without grapefruit juice intake containing the three natural flavonoids, naringenin, quercetin and kaempherol, which are found as glycosides in citrus fruit. These flavonoids interact with the metabolism of drugs such as 17 beta-estradiol and other steroids that are extensively metabolised through the P-450NF (P-450 IIIA4) enzyme or closely related P-450 systems. After administration of grapefruit juice, peak estrone (between 2-6 hours after tablet intake) concentrations increased significantly. The AUC0-48 and AUC0-192 for estrone but not 17 beta-estradiol, resulting from a single administration of micronized 17 beta-estradiol, were significantly altered. Combined measured estrogens (i.e. 17 beta-estradiol and estrone) also increased significantly. The relationship between the AUCs for 17 beta-estradiol and estrone was not altered by juice intake indicating that a metabolic step after estrone, i.e. further A and/or D ring conversion was inhibited. This study demonstrates that grapefruit juice may alter the metabolic degradation of estrogens, and increase the bioavailable amounts of 17 beta-estradiol and its metabolite estrone, presumably by affecting the oxidative degradation of estrogens. This food interaction may be one factor behind the interindividual variability in 17 beta-estradiol, estrone and estriol serum concentrations after exogenous administration of 17 beta-estradiol to patients.
在一项开放性、随机、交叉研究中，对8名卵巢切除术后的女性单次口服2毫克微粉化17β-雌二醇后192小时内血清中17β-雌二醇和雌酮的浓度进行了测量。研究对象在摄入和不摄入含有三种天然黄酮类化合物（柚皮素、槲皮素和山奈酚）的葡萄柚汁的情况下接受研究，这些黄酮类化合物在柑橘类水果中以糖苷形式存在。这些黄酮类化合物会与17β-雌二醇等药物以及其他通过P-450NF（P-450 IIIA4）酶或密切相关的P-450系统进行广泛代谢的类固醇的代谢相互作用。服用葡萄柚汁后，雌酮的峰值浓度（在服药后2至6小时之间）显著升高。单次服用微粉化17β-雌二醇后，雌酮的AUC0-48和AUC0-192（而非17β-雌二醇的）发生了显著变化。联合测量的雌激素（即17β-雌二醇和雌酮）也显著增加。葡萄柚汁的摄入并未改变17β-雌二醇和雌酮的AUC之间的关系，这表明雌酮之后的一个代谢步骤，即进一步的A环和/或D环转化受到了抑制。这项研究表明，葡萄柚汁可能会改变雌激素的代谢降解，并增加17β-雌二醇及其代谢产物雌酮的生物利用量，推测是通过影响雌激素的氧化降解来实现的。这种食物相互作用可能是外源性给予患者17β-雌二醇后，个体间17β-雌二醇、雌酮和雌三醇血清浓度存在差异的一个因素。
