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Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine
Author(s) -
Vincent John,
Harris Stuart I.,
Foulds George,
Dogolo Lisa C.,
Willavize Susan,
Friedman Hylar L.
Publication year - 2000
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2000.00283.x
Subject(s) - amlodipine , grapefruit juice , pharmacokinetics , crossover study , pharmacology , chemistry , pharmacodynamics , volume of distribution , oral administration , blood pressure , placebo , medicine , endocrinology , alternative medicine , pathology
AimsTo determine whether repeated once daily administration of grapefruit juice altered the pharmacokinetics or pharmacodynamics of the calcium antagonist amlodipine.MethodsThe effects of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral and intravenous amlodipine were assessed in 20 healthy men in a placebo‐controlled, open, randomized, four‐way crossover study using single doses of amlodipine 10 mg. For 9 days beginning with the day of administration of amlodipine, grapefruit juice (or water control) was given once daily, and blood samples, blood pressure and heart rate measures were obtained. Plasma concentrations of amlodipine and its enantiomers were determined in separate assays by GC‐ECD.ResultsOral amlodipine had high systemic availability (grapefruit juice: 88%; water: 81%). Pharmacokinetic parameters of racemic amlodipine (AUC, C max , t max , and k el ) were not markedly changed with grapefruit juice coadministration. Total plasma clearance and volume of distribution, calculated after intravenous amlodipine, were essentially unchanged by grapefruit juice (CL 6.65 ml min −1 kg −1 , juice vs 6.93 ml min −1 kg −1 , water; V d ss 22.7 l kg −1 , juice vs 21.0 l kg −1 , water). Grapefruit juice coadministration did not greatly alter the stereoselectivity in amlodipine oral or intravenous kinetics. The sum of S(–) and R(+) enantiomer concentrations correlated well with total racemic amlodipine concentration ( r 2 = 0.957; P = 0.0001). Coadministration of grapefruit juice with either route of amlodipine administration did not significantly alter blood pressure changes vs control.ConclusionsGrapefruit juice has no appreciable effect on amlodipine pharmacodynamics or pharmacokinetics, including its stereoselective kinetics. Bioavailability enhancement by grapefruit juice, noted with other dihydropyridine calcium antagonists, does not occur with amlodipine. Once daily grapefruit juice administration with usual oral doses of amlodipine is unlikely to alter the profile of response in clinical practice.