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Ibuprofen Destroibuprofen
mercial-type reasons.
the
Destrofluoxetine
Under
study
Fluoxetine
Levofluoxetine
On the following pages...
Racemic drugs A large number of drugs on the Levofloxacin: the spectrum is changed 2
the enantiomer is market are racemic mixtures, eg:
not marketed atenolol, warfarin, disopyramide, Levocetirizine: nothing new but the dose 2
atropine, Ca-antagonists,...
Esomeprazole: much ado about nothing 3
Enantiomers Clopidogrel, atorvastatin,
marketed simvastatin, pravastatin, Escitalopram: is it really superior? 4
only as single paroxetine, sertraline, fluticasone,
enantiomers salmeterol, valsartan,...
Conclusions 4
Table 1. Some examples of racemic mixtures and Racemic drugs, enantiomers & Co.
fly-leaf
enantiomers of non-natural origin Bibliography
Levocetirizine = R (-) cetirizine Quite often in the history of antihistamines, it has been observed
Registered indications: similar.
the replacement of old drugs - because of frequent (eg. sedation) or
serious side effects (eg. death from arrhythmia) - with analogues,
Patents and marketing activities: usually metabolites, that are better tolerated or less toxic: ter-
Cetirizine: the patent will expire in
fenadine - for example - was replaced by its active metabolite
2007.
Levocetirizine: it came on to the
fexofenadine. This is not the case of levocetirizine, an active enanti-
market in Italy in 2003. omer of cetirizine.11,12
Levocetirizine was compared with cetirizine only in healthy volun-
teers in order to assess its effective dose: 2.5 and 5 mg of pure en-
antiomer were as effective as 5 and 10 mg respectively of racemic
mixture in reducing the response to intranasal11 and cutaneous12 ad-
ministration of histamine.
Both enantiomers are partially inactivated: S- Omeprazole: it has been marketed as a generic drug since
omeprazole is inactivated to a lesser extent than R- 2001 in the USA, since 2003 in the EU, but in Italy the va-
omeprazole, thus reaching greater blood concentra- lidity of the patent was extended until 2008
(Supplementary Protection Certificate).
tions. At gastric cell level there occurs the transfor-
mation of both isomers in omeprazole-sulfenamide, Esomeprazole: it came on to the market in Italy in 2002
the active metabolite on the proton pump.16,17 with a mutual recognition procedure.
As a result of the different inactivation of the two
enantiomers, administration of 20 mg of esomepra-
zole makes it possible to obtain blood concentra-
tions of the drug (evaluated as area under the
curve or AUC) 70-90% higher than those obtained
by administering 20 mg of the racemic drug.17,18
Due to the higher serum levels obtained, 20 mg of
esomeprazole administered for 5 days cause 90%
suppression of gastric acidity, higher than the 79%
1 Kg vs 1,5 Kg: which one is heavier?
obtained with 20 mg of omeprazole19
On the basis of these figures, it can be said that
14-16 mg of esomeprazole are able to induce
Clinical data: an uneven comparison
an increase in gastric pH similar to that pro-
duced by 20 mg of omeprazole. Despite the availability of basic pharmacological
data, clinical trials were conducted using mainly
In a comparative trial on healthy volunteers, ad-
40 mg of esomeprazole: in practice the choice was
ministration of 40 mg of esomeprazole for 5 days
made to compare relatively higher doses of
maintained gastric pH >4 for 14.0 hours: a higher
esomeprazole in relation to the standard doses
effect if compared to the 12.1 hours obtained with
of the other proton pump inhibitors (PPI).
rabeprazole (20 mg), 11.8 hours with omeprazole
(20 mg), 11.5 hours with lansoprazole (30 mg) and An example of this is the greater effectiveness in the
10.1 hours with pantoprazole (40 mg).20 This supe- treatment of reflux esophagitis found in a systematic
riority was not confirmed in a trial where healthy review comparing esomeprazole with other PPIs22
volunteers treated with 20 mg of esomeprazole for attributable to the use of esomeprazole in higher
5 days showed a less rapid and prolonged gastric doses than the standard doses of the other PPIs.
pH control compared with 20 mg of rabeprazole.21 After 8 weeks of treatment, 40 mg of esomeprazole
achieved an endoscopic cure in 4% more patients
(88% vs. 84%) compared to those treated with
Figure 1. National prescription trend of esomeprazole, ome- standard doses of the other PPIs.
prazole and all the other PPIs (Source: 2005 OsMED Report)
IPP Equivalent doses* Doses on the market
Omeprazole
Omeprazolo Esomeprazole
Esomeprazolo Other IPPs
Altri PPI
Omeprazole 20 mg 10-20 mg
DDD x 1000 inhab/day
12 Lansoprazole 30 mg 15-30 mg
10
8
Pantoprazole 40 mg 20-40 mg
6 Rabeprazole 20 mg 10-20 mg
4
2 Esomeprazole 14 -16 mg 20-40 mg
0
Table 2. Equivalent doses and doses on the market for
2003
Anno
Year
2004 2005
various PPIs. * Equivalence expressed on the basis of
the ability to inhibit gastric acidity
Isomers
different compounds with same
empirical formula, therefore same
atoms in the same quantity
Structural/constitutional Stereoisomers
isomers same atoms and same
same atoms in the same bonds but different
quantity but bonded together in spatial arrangement
a different way
Diastereoisomeris Enantiomers
same atoms, same bonds, same atoms, same bonds
non-mirror but one molecule is the
superimposable non-superimposable
molecules mirror image of the other
Racemic
mixture/raceme
a mixture in equal parts
of 2 enantiomers
Chiral centers
Molecule of levodopa-
mine: the chiral center
is indicated