Farkas Dora, Oleson Lauren E, Zhao Yanli, Harmatz Jerold S, Zinny Miguel A, Court Michael H, Greenblatt David J
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
J Clin Pharmacol. 2007 Mar;47(3):286-94. doi: 10.1177/0091270006298359.
The effect of pomegranate juice (PJ) or grapefruit juice (GFJ) on CYP3A activity was studied in vitro and in healthy human volunteers. In human liver microsomes, the mean 50% inhibitory concentrations (IC(50)) for PJ and GFJ versus CYP3A (triazolam alpha-hydroxylation) were 0.61% and 0.55%, (v/v) respectively, without preincubation of inhibitor with microsomes. After preincubation, the IC(50) for PJ increased to 0.97% (P < .05), whereas the IC(50) for GFJ decreased to 0.41% (P < .05), suggesting mechanism-based inhibition by GFJ but not PJ. Pretreatment of volunteer subjects (n = 13) with PJ (8 oz) did not alter the elimination half-life, volume of distribution, or clearance of intravenous midazolam (2 mg). Administration of PJ also did not affect C(max), total area under the curve (AUC), or clearance of oral midazolam (6 mg). However, GFJ (8 oz) increased midazolam C(max) and AUC by a factor of 1.3 and 1.5, respectively, and reduced oral clearance to 72% of control values. Thus, PJ does not alter clearance of intravenous or oral midazolam, whereas GFJ impairs clearance and elevates plasma levels of oral midazolam.
在体外实验以及健康人类志愿者中研究了石榴汁（PJ）或葡萄柚汁（GFJ）对CYP3A活性的影响。在人肝微粒体中，未经抑制剂与微粒体预孵育时，PJ和GFJ对CYP3A（三唑仑α-羟基化）的平均50%抑制浓度（IC50）分别为0.61%和0.55%（v/v）。预孵育后，PJ的IC50增至0.97%（P < 0.05），而GFJ的IC50降至0.41%（P < 0.05），提示GFJ存在基于机制的抑制作用，而PJ不存在。对13名志愿者受试者用PJ（8盎司）进行预处理，并未改变静脉注射咪达唑仑（2毫克）的消除半衰期、分布容积或清除率。给予PJ也未影响口服咪达唑仑（6毫克）的Cmax、曲线下总面积（AUC）或清除率。然而，GFJ（8盎司）使咪达唑仑的Cmax和AUC分别增加了1.3倍和1.5倍，并使口服清除率降至对照值的72%。因此，PJ不会改变静脉注射或口服咪达唑仑的清除率，而GFJ会损害口服咪达唑仑的清除率并提高其血浆水平。
