The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice
European Journal of Clinical PharmacologyPublished 27 June 1997
C. Clifford, Delyth A Adams, Stephen A. Murray, Graham W. Taylor, Martin R. Wilkins, Alan R. Boobis
Citations69
SJR quartileQ2
SJR score0.85
SNIP1.09
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Administration of grapefruit juice concomitant with terfenadine may lead to an increase in terfenADine bioavailability, but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects, however, this does not exclude the risk of cardiot toxicity in high-risk subjects given greater doses of grape fruit juice over longer periods of time.
Abstract
Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in terfenadine bioavailability, but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects. However, this does not exclude the risk of cardiotoxicity in high-risk subjects given greater doses of grapefruit juice over longer periods of time.
Keywords
Medicine
JAMAMechanism of the Cardiotoxic Actions of Terfenadine
614 Citations1993Raymond L. Woosley
In vitro cardiac electrophysiologic studies found that terfenadine is equipotent to quinidine as a blocker of the delayed rectifier potassium current in isolated feline myocytes, which indicates that episodes of torsades de pointes are most likely the result of a quinidinelike action of the parent drug and of factors that impair the normally rapid metabolism of terfenADine.
The LancetInteraction of citrus juices with felodipine and nifedipine
591 Citations1991Dg Bailey, J. David Spence +2 more
Six men with borderline hypertension took felodipine 5 mg with water, grapefruit juice, or orange juice; the bioavailability with grapefruit Juice was lower, diastolic blood pressure lower, and heart rate higher with Grapefruit juice than with water.
PharmacogeneticsCYP3A gene expression in human gut epithelium
369 Citations1994Joseph C. Kolars, Kenneth S. Lown +6 more
CYP3A4 and CYP3A5 are present throughout the human digestive tract and that differences in the expression of these enzymes may account for inter-organ Differences in the metabolism of CYP 3A substrates.
Clinical Pharmacology & TherapeuticsChanges in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin
366 Citations1992Peter K. Honig, Raymond L. Woosley +3 more
It is concluded that erythromycin alters the metabolism of terfenadine, leading to accumulation of ter Fenadine in certain individuals that is associated with altered cardiac repolarization.
Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel: Lack of prediction by the erythromycin breath test
305 Citations2019Kenneth S. Lown, Joseph C. Kolars +5 more
Carcinogenesis<i>In vitro</i> inhibition of dihydropyridine oxidation and aflatoxin B<sub>1</sub> activation in human liver microsomes by naringenin and other flavonoids
247 Citations1990Frank Peter, Dong‐Hyun Kim
The high concentration of derivatives of naringenin in certain citrus fruits may be of relevance to cancer chemoprevention involving those carcinogens that are activated by cytochrome P-450IIIA4.
Drug Metabolism and DispositionOxidation of the antihistaminic drug terfenadine in human liver microsomes. Role of cytochrome P-450 3A(4) in N-dealkylation and C-hydroxylation.
229 Citations1993Chul‐Ho Yun, Richard A. Okerholm +1 more
Evidence is provided that P- 450 3A4 (and possibly other P-450 3A enzymes) play a major role in the oxidation of (both enantiomers of) terfenadine to both of its major oxidation products.
Clinical Pharmacology & TherapeuticsEffect of grapefruit juice and naringin on nisoldipine pharmacokinetics
189 Citations1993David G. Bailey, J. Malcolm O. Arnold +3 more
Current information supports the cautioning of patients about concomitant ingestion of grapefruit juice and nisoldipine, and the interaction could not be predicted from baseline pharmacokinetics with water and resulted in greater interindividual variability.
ScienceMolecular Genetic Insights into Cardiovascular Disease
186 Citations1996Mark T. Keating, Michael C. Sanguinetti
Genetic testing is now available for a subset of inherited cardiovascular diseases, and new mechanism-based therapies may be available in the near future.
Clinical Pharmacology & TherapeuticsGrapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram*
182 Citations1996Robert Benton, Peter K. Honig +3 more
To establish whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by concomitant administration of grapefruit juice and to determine whether any effect of grape fruit juice is dependent on the timing of administration in relation to the dose of ter Fenadine.
Clinical Pharmacology & TherapeuticsThe effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients
124 Citations1995A. A. M. J. Hollander, Jeroen van Rooij +7 more
To estimate the effect of grapefruit juice on cyclosporine and prednisone metabolism, a large amount of data is needed to estimate the concentration of these drugs in fruit juice.
Clinical Pharmacology & TherapeuticsGrapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans
122 Citations1991P.A. Soons, Birgit A. P. M. Vogels +7 more
There were no consistent effects on blood pressure with all treatments, but in most subjects there was a small temporary increase in heart rate after intake of nitrendipine, and cimetidine did not affect these hemodynamic parameters and did not cause additional adverse effects.
European Journal of Clinical PharmacologyAcute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine ? and its potential clinical relevance
116 Citations1992B. Edgar, David G. Bailey +3 more
The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the diHydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs.
Journal of Chromatography B Biomedical Sciences and ApplicationsDetermination of terfenadine and terfenadine acid metabolite in plasma using solid-phase extraction and high-performance liquid chromatography with fluorescence detection
72 Citations1991John E. Coutant, Patricia A. Westmark +3 more
The use of solid-phase extraction allows the use of robotic or manual sample preparation for the efficient clean-up of terfenadine and terfenADine acid metabolite from plasma.
Journal of ElectrocardiologyTorsade de pointes induced by terfenadine in a patient with long QT syndrome
42 Citations1994Kwang Kon Koh, M. Rim +2 more
The authors report a case of torsade de pointes in a patient with a possible congenital sporadic form of QT interval prolongation who was receiving a therapeutic dose of terfenadine.
Journal of Pharmaceutical SciencesRadioimmunoassay for terfenadine in human plasma
25 Citations1980C. E. Cook, David L. Williams +5 more
Analysis of plasma samples from human subjects given terfenadine showed marked intersubject variability and low plasma levels, and extraction eliminated essentially all of these compounds.