Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation.
1. Felodipine 10 mg extended release was administered with 250 ml regular-strength grapefruit juice or water in a randomized crossover manner followed by a second grapefruit juice treatment in 12 healthy men. The pharmacokinetics of felodipine and primary oxidative metabolite, dehydrofelodipine, were evaluated. 2. Initial grapefruit juice treatment increased felodipine AUC (mean +/- s.d.; 56.6 +/- 21.9 vs 28.1 +/- 11.5 ng ml-1 h; P < 0.001) and Cmax (8.1 +/- 2.5 vs 3.3 +/- 1.2 ng ml-1; P < 0.001) compared with water. Felodipine tmax (median; 2.8 vs 3.0 h) and t1/2 (7.3 +/- 3.7 vs 6.9 +/- 3.6 h) were not altered. 3. Readministration of felodipine with grapefruit juice produced mean felodipine AUC (61.5 +/- 32.2 ng ml-1 h) and Cmax (8.4 +/- 4.8 ng ml-1) which were similar to the initial grapefruit juice treatment 1-3 weeks previously. Felodipine AUC (r = 0.73, P < 0.01) and Cmax (r = 0.69, P < 0.02) correlated between grapefruit juice treatments among individuals. 4. The % increase in felodipine AUC with the initial grapefruit juice treatment compared with water correlated with the % increase in felodipine Cmax among individuals (r = 0.80, P < 0.01). Dehydrofelodipine AUC (74.7 +/- 28.7 vs 48.5 +/- 16.3 ng ml-1 h; P < 0.01) and Cmax (12.1 +/- 2.9 vs 7.9 +/- 2.6 ng ml-1; P < 0.01) were augmented with grapefruit juice compared with water.(ABSTRACT TRUNCATED AT 250 WORDS)
Bailey
D G
DG
Victoria Hospital, University of Western Ontario, London, Canada.
Arnold
J M
JM
Bend
J R
JR
Tran
L T
LT
Spence
J D
JD
D000328:Adult; D000704:Analysis of Variance; D001628:Beverages; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002957:Citrus / Q000737:chemistry; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D015736:Felodipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D018565:Food-Drug Interactions; D006801:Humans; D016014:Linear Models; D008297:Male; D015203:Reproducibility of Results; D044465:White People
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; C081790:dehydrofelodipine; D015736:Felodipine