Dresser G K, Bailey D G, Carruthers S G
Department of Medicine and Pharmacology and Toxicology, London Health Sciences Centre and University of Western Ontario, Canada.
Clin Pharmacol Ther. 2000 Jul;68(1):28-34. doi: 10.1067/mcp.2000.107524.
Grapefruit juice can increase the oral bioavailability of a broad range of medications. This interaction has not been assessed in the elderly.
Twelve healthy elderly people (70 to 83 years of age) were administered 5 mg felodipine extended release with 250 mL grapefruit juice or water in a single-dose study. Subsequently, 6 of these people received 2.5 mg felodipine for 2 days, followed by 5 mg felodipine for 6 days with 250 mL grapefruit juice or water in a steady-state study. Plasma concentrations of felodipine and dehydrofelodipine metabolite, blood pressure, and heart rate were measured over 24 hours after single and final steady-state dose.
Mean felodipine area under the curve and maximum concentration were 2.9-fold and 4.0-fold greater, respectively, with grapefruit juice in both studies. Interindividual variability in the extent of the interaction was high. Felodipine apparent elimination half-life was not altered. Dehydrofelodipine area under the curve and maximum concentration were increased and dehydrofelodipine/felodipine area under the curve ratio was reduced. Systolic and diastolic blood pressures were lower with grapefruit juice in the single-dose study, whereas they were not different between treatments in the steady-state study. Curvilinear relationships existed between plasma felodipine concentration and changes in systolic and diastolic blood pressures. Heart rates were higher with grapefruit juice in both studies; however, this effect was greater and more prolonged at steady state.
A normal dietary amount of grapefruit juice produced a pronounced, unpredictable, and sustained pharmacokinetic interaction with felodipine by reducing its presystemic metabolism in the elderly. The different blood pressure results between the studies can be explained by felodipine concentration-blood pressure response relationships. The elderly should be particularly cautioned about concomitant grapefruit juice and felodipine ingestion.
葡萄柚汁可提高多种药物的口服生物利用度。这种相互作用在老年人中尚未得到评估。
在一项单剂量研究中，给12名健康老年人（70至83岁）服用5毫克非洛地平缓释片，同时饮用250毫升葡萄柚汁或水。随后，其中6人在一项稳态研究中先服用2.5毫克非洛地平2天，接着服用5毫克非洛地平6天，同时饮用250毫升葡萄柚汁或水。在单次和最终稳态剂量后的24小时内测量非洛地平及脱氢非洛地平代谢物的血浆浓度、血压和心率。
在两项研究中，饮用葡萄柚汁时非洛地平的曲线下平均面积和最大浓度分别高出2.9倍和4.0倍。相互作用程度的个体间变异性较高。非洛地平的表观消除半衰期未改变。脱氢非洛地平的曲线下面积和最大浓度增加，脱氢非洛地平/非洛地平曲线下面积比值降低。在单剂量研究中，饮用葡萄柚汁时收缩压和舒张压较低，而在稳态研究中各治疗组之间无差异。血浆非洛地平浓度与收缩压和舒张压变化之间存在曲线关系。在两项研究中，饮用葡萄柚汁时心率均较高；然而，这种效应在稳态时更大且持续时间更长。
正常饮食量的葡萄柚汁通过减少老年人非洛地平的首过代谢，与非洛地平产生了显著、不可预测且持续的药代动力学相互作用。两项研究中不同的血压结果可通过非洛地平浓度 - 血压反应关系来解释。应特别告诫老年人同时摄入葡萄柚汁和非洛地平。
