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Pharmacokinetic properties
Absorption and distribution
Esomeprazole is acid labile and is administered orally as enteric-coated granules. In vivo conversion
to the R-isomer is negligible. Absorption of esomeprazole is rapid, with peak plasma levels occurring
approximately 1-2 hours after dose. The absolute bioavailability is 64% after a single dose of 40 mg and
increases to 89% after repeated once-daily administration. For 20 mg esomeprazole the corresponding
values are 50% and 68%, respectively. The apparent volume of distribution at steady state in healthy
subjects is approximately 0.22 L/kg body weight. Esomeprazole is 97% plasma protein bound.
Food intake both delays and decreases the absorption of esomeprazole although this has no significant
influence on the effect of esomeprazole on intragastric acidity.
Metabolism and excretion
Esomeprazole is completely metabolised by the cytochrome P450 system (CYP). The major part of the
metabolism of esomeprazole is dependent on the polymorphic CYP2C19, responsible for the formation
of the hydroxy- and desmethyl metabolites of esomeprazole. The remaining part is dependent on
another specific isoform, CYP3A4, responsible for the formation of esomeprazole sulphone, the main
metabolite in plasma.
The parameters below reflect mainly the pharmacokinetics in individuals with a functional CYP2C19
enzyme, extensive metabolisers.
Total plasma clearance is about 17 L/h after a single dose and about 9 L/h after repeated
administration. The plasma elimination half-life is about 1.3 hours after repeated once-daily dosing.
The pharmacokinetics of esomeprazole has been studied in doses up to 40 mg b.i.d. The area under
the plasma concentration-time curve increases with repeated administration of esomeprazole. This
increase is dose-dependent and results in a more than dose proportional increase in AUC after
repeated administration. This time - and dose-dependency is due to a decrease of first pass metabolism
and systemic clearance probably caused by an inhibition of the CYP2C19 enzyme by esomeprazole
and/or its sulphone metabolite. Esomeprazole is completely eliminated from plasma between doses
with no tendency for accumulation during once-daily administration.
The major metabolites of esomeprazole have no effect on gastric acid secretion. Almost 80% of an oral
dose of esomeprazole is excreted as metabolites in the urine, the remainder in the faeces. Less than 1%
of the parent drug is found in urine.
Special patient populations
Approximately 2.9±1.5 % of the population lack a functional CYP2C19 enzyme and are called poor metabolisers. In these individuals the metabolism of esomeprazole is probably mainly catalysed by
CYP3A4. After repeated once-daily administration of 40 mg esomeprazole, the mean area under the
plasma concentration-time curve was approximately 100% higher in poor metabolisers than in subjects
having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations
were increased by about 60%. These findings have no implications for the posology of esomeprazole.
The metabolism of esomeprazole is not significantly changed in elderly subjects (71-80 years of age).
Following a single dose of 40mg esomeprazole the mean area under the plasma concentration-time
curve is approximately 30% higher in females than in males. No gender difference is seen after repeated
once-daily administration. These findings have no implications for the posology of esomeprazole.
Impaired organ function
The metabolism of esomeprazole in patients with mild to moderate liver dysfunction may be impaired.
The metabolic rate is decreased in patients with severe liver dysfunction resulting in a doubling of the
area under the plasma concentration-time curve of esomeprazole. Therefore, a maximum of 20 mg
should not be exceeded in patients with severe dysfunction. Esomeprazole or its major metabolites do
not show any tendency to accumulate with once-daily dosing.
No studies have been performed in patients with decreased renal function. Since the kidney is
responsible for the excretion of the metabolites of esomeprazole but not for the elimination of the parent
compound, the metabolism of esomeprazole is not expected to be changed in patients with impaired
renal function.
Adolescents 12-18 years:
Following repeated dose administration of 20mg and 40mg esomeprazole, the total exposure (AUC) and
the time to reach maximum plasma drug concentration (tmax) in 12 to 18 year-olds was similar to that in
adults for both esomeprazole doses.
List of excipients
Glycerol monostearate 40-55, hyprolose, hypromellose, iron oxide (20mg and 40mg tablets: reddish-brown, 20mg tablets: yellow) (E 172), magnesium stearate, methacrylic acid ethyl acrylate copolymer
(1:1) dispersion 30 percent, cellulose microcrystalline, synthetic paraffin, macrogols, polysorbate 80,
crospovidone, sodium stearyl fumarate, sugar spheres (sucrose and maize starch), talc, titanium
dioxide (E 171), triethyl citrate.
Instructions for use and handling
Administration through gastric tube
1. Put the tablet into an appropriate syringe and fill the syringe with approximately 25ml of water and
approximately 5ml air. For some tubes, dispersion in 50ml water is needed to prevent the pellets
from clogging the tube.
2. Immediately shake the syringe for approximately 2 minutes to disperse the tablet.
3. Hold the syringe with the tip up and check that the tip has not clogged.
4. Attach the syringe to the tube whilst maintaining the above position.
5. Shake the syringe and position it with the tip pointing down. Immediately inject 5-10ml into the tube.
Invert the syringe after injection and shake (the syringe must be held with the tip pointing up to avoid
clogging of the tip).
6. Turn the syringe with the tip down and immediately inject another 5-10ml into the tube. Repeat this
procedure until the syringe is empty.
7. Fill the syringe with 25ml of water and 5ml of air and repeat step 5 if necessary to wash down any
sediment left in the syringe. For some tubes, 50ml water is needed.
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