CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012
AFRICA
273
Letter to the Editor
Dear Sir
The letter by Mullier
1
in response to our article titled ‘The grape-
fruit: an old wine in a new glass? Metabolic and cardiovascular
perspectives’
2
refers. The author states that amiodarone is not
only a prodrug but also has inherent pharmacodynamic effects,
just like its metabolite N-desethyamiodarone (N-DEA), which
he correctly suggests could have even greater pharmacological
effects than the parent compound. However, we need to
emphasise that even though N-DEA has similar class III anti-
arrythmic effects, it has faster sodium channel blockade and
lower class IV effects than amiodarone.
3-8
The inhibition of pre-hepatic/hepatic CYP3A4 metabolism of
amiodarone alters both plasma and cardiac substrate:metabolite
ratios. It therefore reduces alterations of PR and QT
C
intervals,
9
and hence diminishes the anti-arrythmic effects of amiodarone.
Both amiodarone and N-DEA have long half-lives (50 and 60
days, respectively),
10-12
and at normal therapeutic doses, the
relative contribution of either to the anti-arrythmic and overall
cardiac electrophysiological effects is not presently known,
despite the aforementioned interaction with grapefruit juice.
This, however, does not disqualify amiodarone as a prodrug.
The interaction of grapefruit juice with amiodarone is more
complicated than previously thought. Naringenin, the naringin
(the predominant flavonoid in grapefruit juice) aglycone, has
recently been reported to prolong QT
C
by inhibiting the rapid
component of delayed rectifier K
+
current (
I
kr
), leading to
significant QT prolongation in healthy subjects and in patients
with dilated or hypertensive cardiomyopathy,
13
as well as in
experimental conditions.
14
It is therefore envisaged that the
pro-arrythmic actions of naringin or grapefruit juice, just like all
class III anti-arrythmic agents, may put patients with myocardial
structural disorders at risk of provoking torsades des pointes.
Even though cases of QT prolongation and torsades de
pointes with amiodarone are rare, a case has been reported of
a female patient who presented with marked QT prolongation
associated with ventricular arrhythmias including torsades de
pointes, requiring electrical cardioversion after amiodarone
administration, after she had been drinking large quantities
of among others grapefruit juice.
15
Perhaps we should have
included these references in our previous article to emphasise the
fact that the interaction between grapefruit juice and amiodarone
is more elaborate than previously thought. We thank the author
for pointing out the typing errors in our references.
PMO Owira, BSc, Med Hons (UCT), MSc (Medicine) (UCT),
PhD (Pharmacology) (UKZN),
References
1.
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Cardiovasc J
Afr
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(1): 37.
2.
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2010;
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: 280–285
.
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