Grapefruit juice--felodipine interaction in the elderly.
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.
Dresser
G K
GK
Department of Medicine and Pharmacology and Toxicology, London Health Sciences Centre and University of Western Ontario, Canada.
Bailey
D G
DG
Carruthers
S G
SG
D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019540:Area Under Curve; D001628:Beverages; D001794:Blood Pressure / Q000187:drug effects*; D002957:Citrus; D003971:Diastole / Q000187:drug effects; D015736:Felodipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011187:Posture; D012016:Reference Values; D013599:Systole / Q000187:drug effects; D013997:Time Factors
D000959:Antihypertensive Agents; C081790:dehydrofelodipine; D015736:Felodipine