PANTOPRAZOLE

PORF. MOKHTAR AL-

GHORAFI
Stereoche*
mistry
Benefits Of Knowing Chirality And Separation Of
Isomer

*Increase receptor selectivity and

potency.
*Decrease adverse effects.
*Decrease dose given to patient.
*Decrease potential drug-drug
interaction.
* Increase safety margin.
Configuratio
n
Pantoprazole
*S(-)& R(+) * Pantoprazole, a selective and long-acting PPI, is
Pantoprazole achiral sulfoxide that is used clinically as a racemic
mixture S-pantoprazole and R(+) pantoprazole.
Animal studies have shown that S-pantoprazole is
more potent (1.5–1.9 times) and effective (3–4times)
than racemate in inhibiting gastric lesions. In human
patients, 20 mg of S-pantoprazole would be at least
equivalent in efficacy to 40 mg of racemic
pantoprazole .
* The S-isomer of pantoprazole was found to be a
better at inhibiting acid related lesions because of its
stronger inhibition of acid secretion. It is also used in
absolute risk reductions for heartburn, acid
regurgitation, and bloating. The pharmacokinetics of
R and S isomers of pantoprazole vary widely in
extensive and poor metabolizers. The use of one
compound avoids this variation and offers sure
material medical
 Pantoprazole
* pantoprazole Pantoprazole,, aa proton
as
as aa racemic
proton pump
racemic mixture.
pump inhibitor,
mixture. To
inhibitor, is
To determine
determine the
is administered
administered
the role
role of
of
cytochrome
cytochrome P450
P450 (CYP)
(CYP) 2C19
2C19 in
in the
the stereo
stereo selective
selective
metabolism
metabolism of of pantoprazole,
pantoprazole, we
we investigated
investigated the
the
pharmacokinetic
pharmacokinetic disposition
disposition of
of (+)-
(+)- and
and (–)-pantoprazole
(–)-pantoprazole
in
in 77 extensive
extensive metabolizers
metabolizers and
and 77 poor
poor metabolizers
metabolizers of of S-
S-
mephenytoin.
mephenytoin. AllAll of
of the
the subjects
subjects received
received an
an oral
oral 40-mg
40-mg
dose
dose ofof racemic
racemic pantoprazole
pantoprazole asas the
the enteric-coated
enteric-coated
formulation.
formulation.
In
In the
the extensive
extensive METABOLIZERS,
METABOLIZERS, the the mean
mean clearance
clearance
of
of (–)-pantoprazole
(–)-pantoprazole was
was only
only slightly
slightly lower
lower than
than that
that of
of
(+)-pantoprazole
(+)-pantoprazole and
and no
no significant
significant differences
differences inin the
the
other
other pharmacokinetic
pharmacokinetic parameters
parameters between
between (+)-
(+)- and
and (–)-
(–)-
pantoprazole
pantoprazole were
were observed.
observed. The
The mean
mean (+)/
(+)/ (–)
(–) ratios
ratios for
for
maximum
maximum concentration,
concentration, area
area under
under the
the plasma
plasma
concentration-time
concentration-time curve
curve from
from 00 to
to infinity
infinity ,, and
and
elimination
elimination half-life
half-life were
were 0.94,
0.94, 0.82,
0.82, and
and 0.90,
0.90,
respectively.
respectively.
*3D structure of In
In contrast,
contrast, in
in the
the poor
poor metabolizers,
metabolizers, the
the clearance
clearance

pantoprazole
values
values of
of both
both enantiomers
enantiomers were
were significantly
significantly lower
lower
than
than those
those in
in the
the extensive
extensive metabolizers,
metabolizers, and
and a
a
significant
significant difference
difference in
in pharmacokinetics
pharmacokinetics between
between
(+)-
(+)- and
and (–)-pantoprazole
(–)-pantoprazole waswas observed.
observed. The
The mean
mean
elimination
elimination half-life
half-life for
for (+)-pantoprazole
(+)-pantoprazole was
was 3.55-
3.55-
fold
fold longer
longer than
than that
that of
of (–)-
(–)- pantoprazole,
pantoprazole, and
and the
the
mean
mean maximum
maximum concentration
concentration and
and area
area under
under the
the
plasma
plasma concentration-time
concentration-time curve
curve from
from 00 to
to infinity
infinity
for
for (+)-pantoprazole
(+)-pantoprazole were
were 1.31-
1.31- and
and 3.59-fold
3.59-fold greater,
greater,
respectively,
respectively, than
than those
those for
for (–)-pantoprazole.
(–)-pantoprazole. These
These
results
results indicate
indicate that
that the
the stereoselective
stereoselective metabolism
metabolism of
of
pantoprazole
pantoprazole depends
depends onS-mephenytoin
onS-mephenytoin 4'-
4'-
hydroxylase
hydroxylase (CYP2C19).
(CYP2C19). The
The metabolism
metabolism of
of (+)-
(+)-
pantoprazole
pantoprazole was
was impaired
impaired to
to a
a greater
greater extent
extent than
than
(–)-pantoprazole
(–)-pantoprazole in
in the
the poor
poor metabolizers
metabolizers
pantoprazole
 ?What is pantoprazole

is a proton pump
inhibitor that decreases
the amount of acid
produced in the stomach
and decreased gastric
secreation, it works by
inactivating (H+\K+)-
ATPase function in the
stomach..
Uses and Administration
Uses and Administration
Adverse effects
The most common side effects with pantoprazole
include

 Headache
 Diarrhea
 Nausea
 Stomach pain
 Vomiting
 Gas
 Dizziness
 Pain in your joints
Administration in hepatic impairment
Dosage of pantoprazole may need to be reduced in severe hepatic
impairment, or doses given only on alternate days. A maximum dose of 20
mg daily orally or intravenously, or 40 mg orally on alternate days, has
been suggested. Doses above 40 mg daily have not been studied in
patients with hepatic impairment. Liver enzymes should be monitored
during therapy, and pantoprazole should be stopped if elevations occur

Administration in renal impairment

 
Most studies have not found the pharmacokinetics of pantoprazole to be
altered in patients with renal impairment1 and licensed drug information in
the UK and US generally does not recommend dosage adjustment in this
group; however some UK sources, including the BNF, suggest that a maximum
dose of 40 mg daily should be observed
 Pantoprazole Drug Interaction

View interaction of pantoprazole with

Levothyroxine,Atorvastatin,Naproxen,Clopidogreland
.. Asprin

 
Warnings

Kidney conditions Bacterial infections

Bone problems Skin problems

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