Eur J Clin Pharmacol. 2005 Mar 11.
Enalapril dosage in progressive chronic nephropathy:
a randomised, controlled trial.
Elung-Jensen T, Heisterberg J, Sonne J, Strandgaard S,
Kamper AL.
Departments of Nephrology and Clinical Physiology and Nuclear Medicine,
Herlev Hospital, University of Copenhagen, Denmark.
OBJECTIVE: In chronic renal failure, clearance of enalapril is reduced.
Hence, a renoprotective effect may be achieved with lower doses than conventionally
used. Since marked inter-patient variation in concentrations of enalaprilat
has been shown in patients with renal failure despite equivalent dosage
of enalapril, a direct comparison of the effect of high versus low plasma
concentrations of enalaprilat on the progression of renal failure was undertaken.METHODS:
Forty patients with a median glomerular filtration rate (GFR) of 17 (6-35)
ml/min/1.73 m(2) were studied in an open-label, randomised trial comparing
patients with a high (>50 ng/ml) with patients with a low (<10 ng/ml)
target trough plasma concentration of enalaprilat. The dose of enalapril
was titrated accordingly. The patients were followed for 12 months or until
they needed renal replacement therapy. GFR was measured at 3-month intervals
by the plasma clearance of (51) Cr-EDTA, and the individual rates of progression
of renal failure were calculated as the slope of GFR versus time plot.RESULTS:
In the high-concentration group, the median enalaprilat trough concentration
was 92.9 ng/ml (21.8-371.0 ng/ml) and in the low-concentration group it
was 9.1 ng/ml (2.5-74.8 ng/ml) at 3 months follow-up (P<0.001). The median
daily doses of enalapril were 10 mg (2.5-30 mg) and 1.88 mg (1.25-5 mg)
in the high and low groups, respectively (P<0.001). In the high-concentration
group, the mean+/-SE decline in renal function was 6.1+/-1.5 ml/min/1.73
m(2) per year and in the low-concentration group it was 4.3+/-14.4 ml/min/1.73
m(2) per year (P=0.48). Five patients in the high-concentration group reached
end-stage renal failure whereas none in the low-concentration group did
(P=0.04). There were no statistically significant differences in blood pressure
level, concomitant antihypertensive therapy or urinary albumin excretion.
However, the high-enalaprilat concentration group had an overall higher
plasma potassium concentration of 0.42 mmol/l than the low group (P<0.001).CONCLUSION:
In patients with moderate to severe renal insufficiency, a low concentration
of enalaprilat afforded the same degree of renoprotection, blood pressure
control and minimisation of proteinuria as a high concentration, during
12 months of follow-up. The high-dosage treatment was associated with a
more pronounced tendency to hyperkalaemia. Thus, there seems to be no indication
for increasing the daily dose of enalapril beyond what achieves adequate
blood pressure control in this group of patients.
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J Pharm Biomed Anal. 2005 Mar 9;37(3):627-30.
Epub 2004 Dec 25.
Quantitative analysis of enalapril by (1)H NMR spectroscopy
in tablets.
Zoppi A, Linares M, Longhi M.
Departamento de Farmacia, Facultad de Ciencias Quimicas, Universidad Nacional
de Cordoba, Ciudad Universitaria, 5000 Cordoba, Argentina.
A simple, rapid, accurate and selective (1)H NMR method was developed
for quantitative determination of enalapril maleate in pharmaceutical
preparations. Spectra were determined in D(2)O, using l-leucine as internal
standard. Both synthetic mixtures and commercial dosage forms were assayed,
and the results were compared to those obtained using the USP XXIV procedure
and were both in close agreement. |
| GENERIC NAME: enalapril
BRAND NAME: Vasotec
DRUG CLASS AND MECHANISM: Enalapril is an ACE (angiotensin
converting enzyme) inhibitor. ACE is an enzyme in the body which is important
for the formation of angiotensin II. Angiotensin II causes constriction
of arteries in the body, thereby elevating blood pressure. ACE inhibitors,
such as enalapril, lower blood pressure by inhibiting the formation of
angiotensin II, thus relaxing the arteries. Relaxing the arteries not
only lowers blood pressure, but also improves the pumping efficiency of
a failing heart and improves cardiac output in patients with heart failure.
PREPARATIONS: tablets: 2.5 mg, 5 mg, 10 mg, 20 mg.
STORAGE: Tablets should be stored at room temperature
in a tightly closed container.
PRESCRIBED FOR: Enalapril can be used alone in treating
high blood pressure. Its blood pressure lowering effect can be further
enhanced by the addition of a diuretic medication. Vaseretic is an example
of a medication that combines the effect of enalapril with a thiazide-type
diuretic (water pill) to reduce blood pressure. By reducing resistance
in the arteries, enalapril can be useful in the treatment of congestive
heart failure. In treating heart failure, enalapril usually supplements
conventional treatment, including a diuretic and digoxin (Lanoxin). After
a heart attack, enalapril has been found to be effective in improving
functioning of the damaged heart, and in reducing symptoms and hospitalizations
related to heart failure.
PROPER USE: Should be taken on an empty stomach one
hour before meals.
PRECAUTIONS: Enalapril should not be taken by people
with a known allergy to ACE inhibitors. Swelling of the facial tissues
and even the upper airways has been reported with ACE inhibitors on very
rare occasions, and can lead to serious breathing difficulties. Enalapril
can interact with diuretics (water pills) and other blood pressure medicines
to cause an excessive drop in blood pressure, which can cause symptoms
of weakness, dizziness, and lightheadedness. Impairment of kidney function
has been reported with ACE inhibitors, especially in patients with severe
heart failure or pre-existing kidney disease.
Combining enalapril with potassium supplements, potassium containing
salt substitutes, and potassium-conserving diuretics such as amiloride
(Moduretic), spironolactone (Aldactone), and triamterene (Dyazide, Maxzide),
can lead to dangerously high blood levels of potassium.
In rare instances, low white blood cell counts have been reported with
the use of captopril, another ACE inhibitor. Low white blood cells increase
the patient's risk of infections. When taken with lithium, enalapril can
increase lithium to toxic levels in the blood. Safe use in children is
not established. It is not habit forming.
PREGNANCY: ACE inhibitors, including enalapril, can
be harmful to the fetus and should not be taken by pregnant women.
NURSING MOTHERS: ACE inhibitors, including enalapril,
should be avoided in nursing mothers.
SIDE EFFECTS: Enalapril is generally well tolerated
and side effects are usually mild and transient. A dry, persistent cough
has been reported with the use of ACE inhibitors. Coughing resolves after
discontinuing the medication. Other side effects are rare and include
abdominal pain, diarrhea, dizziness, fatigue, headache, loss of appetite,
nausea and vomiting, chest pain, severe dizziness or fainting, numbness
or tingling in the hands or feet, rash, and a sore or swollen throat.
In rare instances, liver dysfunction and skin yellowing (jaundice) have
been reported with ACE inhibitors.
Caution!Before starting
to take this medicine, it is vital that you should consult your doctor!
Do not use it on your own initiative, without medical advice.
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