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Grapefruit juice–felodipine interaction in the elderly
Author(s) -
Dresser George K.,
Bailey David G.,
Carruthers S. George
Publication year - 2000
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2000.107524
Subject(s) - felodipine , grapefruit juice , pharmacokinetics , bioavailability , chemistry , pharmacology , metabolite , area under the curve , active metabolite , blood pressure , medicine , endocrinology , biochemistry
Background Grapefruit juice can increase the oral bioavailability of a broad range of medications. This interaction has not been assessed in the elderly. Methods 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. Results 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. Conclusions 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. Clinical Pharmacology & Therapeutics (2000) 68 , 28–34; doi: 10.1067/mcp.2000.107524