Monograph: |
Carnitine
Levocarnitine
White odourless, hygroscopic crystals or crystalline powder.
Freely soluble in water and hot alcohol; practically insoluble
in acetone and in ether. A 5% solution in water has a pH of
6.5 to 8.5. Store in airtight containers.
Adverse Effects
Gastro-intestinal disturbances such as nausea, vom-
iting, diarrhoea, and abdominal cramps have been
reported following the administration of L-carnitine.
Body odour has also been noticed in some patients.
Of 30 patients given DL-carnitine intravenously after dialysis
sessions 3 developed myasthenia-like symptoms but follow-
ing administration of only L-carnitine to these 3 the symptoms
did not occur. t It was considered that in anuric, uraemic pa-
tients the D-isomer was not excreted adequately and that ac-
cumulation had blocked neuromuscular transmission. It was
therefore suggested that L-carnitine. rather than the Dt-form,
should be employed.
Uses and Administration
L-Carnitine is an amino acid derivative which is an
essential cofactor of fatty acid metabolism.
Carnitine is used in the treatment of primary carni-
tine deficiency and has also been tried in carnitine
deficiency secondary to a variety of defects of inter-
mediary metabolism or other conditions such as
haemodialysis. Both the L- and the DL-isomers have
been used. but it is believed that only L-carnitine is
effective and in addition, that DL-carnitine supple-
mentation can lead to carnitine deficiency.
In primary carnitine deficiency, up to 200 mg per kg
body-weight daily by mouth may be required, ad-
ministered in 2 to 4 divided doses. Rarely, higher
doses of up to 400 mg per kg daily may be needed.
When administered intravenously, up to 100 mg per
kg daily is given in 3 to 4 divided doses by slow in-
travenous injection over 2 to 3 minutes.
In patients with carnitine deficiency secondary to
haemodialysis, the recommended dose is 20 mg per
kg intravenously after each dialysis session, adjust-
ed according to plasma-carnitine concentrations. A
maintenance dose of I g daily by mouth may be
considered.
Carnitine is under investigation for the treatment of
zidovudine-induced mitochondrial myopathy.
Carnitine hydrochloride, carnitine orotate, and bi-
canutine chloride have also been used.
Carnitine, which has been the subject of several reviews.
occurs in distinct L- and o-isomere although naturally-occur-
ring carnitine is almost exclusively the L-isomer. In higher
animals carnitine is an essential co-factor of fatty acid metab-
olism in the heart, liver, and skeletal muscle. It is normally
synthesised in the liver, brain, and kidneys in sufficient quan-
tities to meet human requirements but dietary sources such as
meat and dairy products also provide carnitine. In plasma and
tissues carnitine is present in the free form and as acylcami-
line esters of which acetylcarnitine is the most abundant.
It has been pointed out that L-carnitine should be used in ther-
apeutics in preference to DL-carnitine, which is the form often
present in over-the-counter preparations and dietary supple-
profiles of the two isomers are very different with L-carnitine
acting as a substrate for carnitine acetyltransferase while D-
carnitine acts as a competitive inhibitor; also, L-carnitine-
induced stimulation of palmitate oxidation is competitively
inhibited by D-palmitoylcarnitine. Such differences in the ac-
tivities of the isomers are thus believed to account lor findings
of benefit only with the L-isomer or unwanted effects when D-
carnitine or DL-carnitine was administered.~
Primary carnitine deficiency is a disorder of the membrane
transport of carnitine and patients have presented with hy-
poglycaemia and encephalopathy, skeletal myopathy, and
cardiomyopathy. Therapy with carnitine in these primary de-
ficiency states is considered to have a rational basis' ~ Sec-
ondary carnitine deficiency occurs in many inherited
metabolic disorders and especially in the organic acidurias
and disorders of beta-oxidation. Some authors have said that
the benefit of therapy with carnitine is limited in organic
acidurias2 and unproven or doubtful in disorders of beta-
oxidation's6 while others have disagreed with this view be-
lieving treatment may be worthwhile.
Carnitine deficiency may also arise during the long-term ad-
ministration of drugs such as valproic acid, pivampicillin.
or pivmecillinam, which are conjugated with carnitine. In-
vestigations are in progress to assess whether carnitine sup-
plementation can prevent or reverse this type of carnitine
deficiency but treatment with carnitine, although it raised
plasma-carnitine concentrations, had no more effect than pla-
cebo on the well-being of children receiving valproic acid
therapy in one such study.
Since camiline supplementation has been associated with a
reduction in the incidence of haemodialysis-induced
cramps it has been suggested that these cramps
might be due in part to carnitine deficiency.
There is also some evidence that carnitine supplements
may be of benefit to low birth-weight preterm infants, but a
double-blind study failed to confirm this effect. However,
premature infants at particular risk of carnitine deficiency.
such as those on long-term parenteral nutrition, may bene-
fit. Some workers consider that carnitine supplements may
be advisable in full-term infants receiving formula feeds.
Low concentrations of carnitine have also been reported to
occur ill a variety of other conditions and there is some evi-
dence that carnitine supplementation may exert a cardiopro-
tective role. Benefit in patients with cardiomyopathies.
reduction of infarct size and prevention of arrhythmias in pa-
tients with myocardial infarction, increased exercise toler-
ance in patients with anginal or intermittent claudication,'
and protection from the cardiotoxicity of the anthracycline
antineoplastics' have ail been described in patients given car-
nitine supplementation. However, the use of carnitine in
healthy subjects in an attempt to improve athletic perform-
ance is controvenial.
A case report has described a dramatic response of long-
standing leg ulcers to carnitine therapy in a patient with
sickle-cell disease.
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