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• W2004243463 abstract "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." @default.
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• W2004243463 date "1999-07-01" @default.
• W2004243463 modified "2023-09-23" @default.
• W2004243463 title "Naringenin and interindividual variability in interaction of coumarin with grapefruit juice" @default.
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• W2004243463 doi "https://doi.org/10.1016/s0940-2993(99)80008-6" @default.
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