Edgar B, Bailey D, Bergstrand R, Johnsson G, Regårdh C G
Astra Cardiovascular Research, Astra Hässle, Mölndal, Sweden.
Eur J Clin Pharmacol. 1992;42(3):313-7. doi: 10.1007/BF00266354.
The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1, and in the AUC from 23 to 65 nmol.h.l-1. The change in AUC corresponded to an increase in the systemic availability of felodipine from 15 to 45%, assuming no change in its clearance. This change was probably caused by inhibition of the oxidation of felodipine to the inactive dehydrofelodipine by flavonoids in grapefruit juice. The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the dihydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs. The higher plasma concentrations of felodipine taken with grapefruit juice resulted in a greater change in blood pressure measured in the morning 3 h after dosing (-9%) than did water (0%).
在9名健康中年男性中研究了饮用葡萄柚汁对服用5毫克普通片剂的二氢吡啶类钙拮抗剂非洛地平急性药代动力学和血流动力学作用的影响。与水相比，葡萄柚汁使非洛地平的Cmax从平均6纳摩尔/升增加到16纳摩尔/升，AUC从23纳摩尔·小时/升增加到65纳摩尔·小时/升。假设非洛地平清除率不变，AUC的变化相当于其全身可用性从15%增加到45%。这种变化可能是由于葡萄柚汁中的类黄酮抑制了非洛地平氧化为无活性的脱氢非洛地平。与葡萄柚汁的相互作用被认为是二氢吡啶类药物的类效应，因为二氢吡啶环氧化为相应的吡啶衍生物是所有这些药物的主要代谢途径。与水相比，服用葡萄柚汁时非洛地平的血浆浓度更高，导致给药后3小时早晨测量的血压变化更大（-9%），而水组为0%。
