Mohri K, Uesawa Y
Department of Pharmaceutics, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
Pharm Res. 2001 Feb;18(2):177-82. doi: 10.1023/a:1011028401189.
It has been reported that grapefruit juice (GJ) causes a pharmacokinetic interaction with many drugs after co-ingestion. It is postulated that the substances in GJ may inhibit the first-pass metabolism during the intestinal absorption process. In recent years, several furanocoumarin derivatives that inhibit P450 activity in intestinal microsomes were isolated from GJ. In this study, we report the effects of the furanocoumarin derivatives in GJ on the nifedipine (NFP) pharmacokinetics in rats.
Three furanocoumarin derivatives (bergaptol [BT], bergamottin [BG], and 6',7'-dihydroxybergamottin [DHB]) found in GJ were used in this study. Each furanocoumarin was reconstituted in orange juice at the same concentration as in the GJ. Two milliliters of each sample was administered into the rat duodenum. After 30 min, NFP was intraduodenally administered at a dose of 3 mg/kg body weight. The NFP concentrations in the plasma samples were determined by HPLC.
A significant increase in the AUC of NFP was observed only in the rats administered BG; 1.5 times that of the control group. The result was quite identical with that of the group that was administered GJ. BT and DHB had no significant effects on the NFP pharmacokinetics.
The results strongly suggested that BG in GJ might be the substance that elevates the NFP plasma concentrations.
据报道，葡萄柚汁（GJ）与多种药物同时摄入后会产生药代动力学相互作用。据推测，GJ中的物质可能会在肠道吸收过程中抑制首过代谢。近年来，从GJ中分离出了几种抑制肠道微粒体中P450活性的呋喃香豆素衍生物。在本研究中，我们报告了GJ中的呋喃香豆素衍生物对大鼠硝苯地平（NFP）药代动力学的影响。
本研究使用了在GJ中发现的三种呋喃香豆素衍生物（佛手柑醇[BT]、香豆素[BG]和6'，7'-二羟基香豆素[DHB]）。每种呋喃香豆素均以与GJ中相同的浓度在橙汁中复溶。将2毫升每个样品经十二指肠给予大鼠。30分钟后，以3毫克/千克体重的剂量经十二指肠给予NFP。通过高效液相色谱法测定血浆样品中的NFP浓度。
仅在给予BG的大鼠中观察到NFP的AUC显著增加；是对照组的1.5倍。结果与给予GJ的组完全相同。BT和DHB对NFP药代动力学没有显著影响。
结果强烈表明，GJ中的BG可能是提高NFP血浆浓度的物质。
