Bourian M, Runkel M, Krisp A, Tegtmeier M, Freudenstein J, Legrum W
Institute of Pharmacology and Toxicology, Philipps University Marburg, Germany.
Exp Toxicol Pathol. 1999 Jul;51(4-5):289-93. doi: 10.1016/S0940-2993(99)80008-6.
Grapefruit juice has been shown to enhance oral bioavailability of several drugs including coumarin. The degree of the interaction is highly variable among the individuals.
The aim of the study was to evaluate the interindividual variability in the pharmacokinetic profile of three components of grapefruit juice (naringin/naringenin, scopoletin, umbelliferone) and to compare it with the pattern of coumarin-grapefruit juice interaction.
A two-set clinical study with the participation of 18 healthy volunteers was designed. In the first set of the experiment the total renal recovery of naringenin, scopoletin and umbelliferone within 13 hours after the intake of 1L grapefruit juice was estimated. Four individuals, who had demonstrated extremely high or extremely low excretion of the metabolites in the first set, were selected for the second set. The subjects took 10 mg coumarin with 1L grapefruit juice vs 10 mg coumarin with 1 L water in a cross-over manner. The interaction pattern was evaluated according to the time-course curves of 7-hydroxycoumarin (main metabolite of coumarin) excreted with urine. The detailed time-course excretory profiles of naringenin and scopoletin from grapefruit juice were also obtained.
The screening demonstrated a significant interindividual variability in the renal excretion of naringenin (max/min > 15), scopoletin (max/min = 6.2), umbelliferone (max/min = 3.3). The interaction between coumarin and grapefruit juice has been observed by increase in the total recovery of 7-hydroxycoumarin up to 3 mg and by delay in time of its excretion by 2-3 hours. This interaction has been observed in 3 of 4 subjects and correlated with naringenin amounts in the urine. The mechanism and the sites of the interaction, as well as the causes for its wide interindividual variability are discussed in the paper.
已证明葡萄柚汁可提高包括香豆素在内的几种药物的口服生物利用度。个体之间相互作用的程度差异很大。
本研究的目的是评估葡萄柚汁三种成分（柚皮苷/柚皮素、东莨菪亭、伞形花内酯）药代动力学特征的个体间变异性，并将其与香豆素 - 葡萄柚汁相互作用模式进行比较。
设计了一项有18名健康志愿者参与的两组临床研究。在第一组实验中，估计摄入1升葡萄柚汁后13小时内柚皮素、东莨菪亭和伞形花内酯的总肾回收率。从第一组中选择了四名代谢物排泄极高或极低的个体进行第二组实验。受试者以交叉方式服用10毫克香豆素与1升葡萄柚汁，以及10毫克香豆素与1升水。根据随尿液排出的7 - 羟基香豆素（香豆素的主要代谢物）的时间进程曲线评估相互作用模式。还获得了葡萄柚汁中柚皮素和东莨菪亭详细的时间进程排泄曲线。
筛选显示柚皮素（最大值/最小值>15）、东莨菪亭（最大值/最小值 = 6.2）、伞形花内酯（最大值/最小值 = 3.3）的肾排泄存在显著的个体间变异性。香豆素与葡萄柚汁之间的相互作用表现为7 - 羟基香豆素的总回收率增加至3毫克，其排泄时间延迟2 - 3小时。在4名受试者中的3名中观察到了这种相互作用，并且与尿液中柚皮素的量相关。本文讨论了相互作用的机制和部位，以及其个体间差异大的原因。
