Dramatic inhibition of amiodarone metabolism induced by grapefruit juice

Libersa, Christian; Brique, Serge A.; Motte, Kokou B.; Caron, Jacques; Guédon-moreau, Laurence M.; Humbert, Luc; Vincent, Anne; Devos, Patrick; Lhermitte, Michel

doi:10.1046/j.1365-2125.2000.00163.x

Cited by 83 publications

(38 citation statements)

References 35 publications

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“…Formation of N-DEA is mediated by CYP3A4 (Fabre et al, 1993). A measure of 300 ml grapefruit juice simultaneously, 3 and 9 h after amiodarone dose, caused a complete inhibition of N-DEA formation (Libersa et al, 2000). The clinical implications of this finding are still unclear and need further investigation.…”

Section: Amiodaronementioning

confidence: 93%

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

2003

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More than a decade has passed since it was unintentionally discovered that grapefruit juice interacts with certain drugs. The coadministration of these drugs with grapefruit juice can markedly elevate drug bioavailability, and can alter pharmacokinetic and pharmacodynamic parameters of the drug. The predominant mechanism for this interaction is the inhibition of cytochrome P-450 3A4 in the small intestine, resulting in a significant reduction of drug presystemic metabolism. An additional mechanism is, presumably, the inhibition of P-glycoprotein, a transporter that carries drug from the enterocyte back to the gut lumen, resulting in a further increase in the fraction of drug absorbed. Some calcium channel antagonists, benzodiazepines, HMG-CoA reductase inhibitors and cyclosporine are the most affected drugs. A single exposure to one glass of the juice can usually produce the maximal magnitude of the interaction. The data available so far, concerning this interaction and its clinical implications, are reviewed in this article. It is likely that more information regarding this interaction will accumulate in the future, and awareness of such is necessary for achieving optimal drug therapy.

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Section: Amiodaronementioning

confidence: 93%

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

2003

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“…The antiarrhythmic agent amiodarone had a mean C max with grapefruit juice (300 mL at 0, 3 and 9 h relative to drug administration) corresponding to 180% of that with water; the AUC was 150% of that with water. 30 The combination was also reported to markedly prolong the corrected QT interval and to cause ventricular ar rhythmias, including torsade de pointes, in clinical practice. 18 Dronedarone, the chemical analog of amiodarone, was associated with reports of ventricular arrhythmia, cardiac arrest and torsade de pointes in clinical practice.…”

Section: Torsade De Pointesmentioning

confidence: 99%

Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?

Bailey

Dresser

Arnold

2012

CMAJ

215

156

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“…This phenomenon is attributed to the suppression of cytochrome P450 enzyme in the small intestine by the components of grapefruit juice, decreasing drug metabolism and thus increasing the drug concentration [31]. A significantly increased area under the curve and maximum concentration of amiodarone has been noted when administered with grapefruit juice [32]. Concomitant administration of grapefruit juice has been shown to reduce the clearance of quinidine and increase its elimination half-life [33].…”

Section: Discussionmentioning

confidence: 99%

The Additive Effects of the Active Component of Grapefruit Juice (Naringenin) and Antiarrhythmic Drugs on HERG Inhibition

Lin

Ke²,

Ranade³

et al. 2007

Cardiology

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Background: Grapefruit juice causes significant QT prolongation in healthy volunteers and naringenin has been identified as the most potent human ether-a-go-go-related gene (HERG) channel blocker among several dietary flavonoids. The interaction between naringenin and I_Kr-blocking antiarrhythmic drugs has not been studied. We evaluated the effect of combining naringenin with I_Kr-inhibiting antiarrhythmic drugs on cardiac I_Kr. Methods and Results:I_Kr current was studied by using HERG expressed in Xenopus oocytes, and the two-electrode voltage clamp technique was employed. Antiarrhythmic drugs (azimilide, amiodarone, dofetilide and quinidine) were tested. Experiments were performed at room temperature. Naringenin blocked HERG current dose dependently with an IC₅₀ of 173.3 ± 3.1 µM. Naringenin 100 µM alone inhibited HERG current by 31 ± 6%, and this inhibitory effect was increased with coadministration of 1 or 10 µM antiarrhythmic drugs. When 100 µM naringenin was added to antiarrhythmic drugs, greater HERG inhibition was demonstrated, compared to the current inhibition caused by antiarrhythmic drugs alone. Addition of naringenin significantly increased current inhibition (p < 0.05). Conclusions: There is an additive inhibitory effect on HERG current when naringenin is combined with I_Kr-blocking antiarrhythmic drugs. This additive HERG inhibition could pose an increased risk of arrhythmias by increasing repolarization delay and possible repolarization heterogeneity.

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Dramatic inhibition of amiodarone metabolism induced by grapefruit juice

Cited by 83 publications

References 35 publications

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

Grapefruit–medication interactions: Forbidden fruit or avoidable consequences?

The Additive Effects of the Active Component of Grapefruit Juice (Naringenin) and Antiarrhythmic Drugs on HERG Inhibition

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