Shafaati, A. (2010). Chiral Drugs: Current Status of the Industry and the Market. Iranian Journal of Pharmaceutical Research, Volume 6(Number 2), 73-74. doi: 10.22037/ijpr.2010.702
A Shafaati. "Chiral Drugs: Current Status of the Industry and the Market". Iranian Journal of Pharmaceutical Research, Volume 6, Number 2, 2010, 73-74. doi: 10.22037/ijpr.2010.702
Shafaati, A. (2010). 'Chiral Drugs: Current Status of the Industry and the Market', Iranian Journal of Pharmaceutical Research, Volume 6(Number 2), pp. 73-74. doi: 10.22037/ijpr.2010.702
Shafaati, A. Chiral Drugs: Current Status of the Industry and the Market. Iranian Journal of Pharmaceutical Research, 2010; Volume 6(Number 2): 73-74. doi: 10.22037/ijpr.2010.702
Chiral Drugs: Current Status of the Industry and the Market
Acute and Subchronic Toxicity?of Teucrium polium Total Extract in Rats
Iranian Journal of Pharmaceutical Research (2007)
6 (2): 73-74
Copyright ? 2005 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services
Editorial
Chiral Drugs: Current Status of the
Industry and the Market
Alireza Shafaati
The biological activity of chiral
substances often depends upon their stereochemistry, since the living body is a
highly chiral environment. A large percentage of commercial and investigational
pharmaceutical compounds are enantiomers, and many of them show significant
enantioselective differences in their pharmacokinetics and pharmacodynamics. The
importance of chirality of drugs has been increasingly recognized, and the
consequences of using them as racemates or as enantiomers has been frequently
discussed in the pharmaceutical literature during recent years. Most of the
chiral drugs are administered as racemates, despite the fact that the optical
isomers of a racemic drug can exhibit different pharmacological profiles in
living systems. These differences can be expressed in e.g. the affinity of the
enantiomers for certain receptor subtypes or enzymes, distribution rates, their
metabolism and excretion, in antagonistic actions relative to each other, or
their toxicological properties. Obviously, the more chiral centres present in a
(drug) molecule, the more complex the situation becomes.
The origin of the discovery of the role of stereochemistry in biochemical
environments dates back to the late 1850?s, when Pasteur reported the different
destruction rates of dextro and levo ammonium tartrate by the mold Penicillium
glaucum. In the conclusion of his observations, Pasteur wrote: ?Most natural
organic products, the essential products of life, are asymmetric and possess
such asymmetry that they are not superimposable on their images.? For some
reason, this knowledge of racemic organic compounds and racemisation seemed to
be forgotten until the question of racemic compounds was raised by Ariens in the
late 1980?s. He asked the question? why we in some cases have to give doses to
the patient where half of the content has no effect or the opposite effect??.
After this rediscovery of stereochemistry, the regulatory authorities defined
more strict requirements on drug discovery and chiral compounds. Besides the
ethical reasons, the therapeutic benefit (efficacy and safety) and, in several
instances, extension of the life cycle of drugs have been the motivation for
developing single enantiomers.
Single?enantiomer drug sales show a continuous growth worldwide and many of the
topselling drugs are marketed as single enantiomers. In this context, there has
been a rapid development of enantioselective synthetic methodologies, which have
now reached a high degree of diversity and complexity. Simultaneously, this new
trend produced a rapid increase in the demand for stereoselective separation
techniques and analytical assays for precise determination of the enantiomeric
purity of chiral compounds. The development of chiral stationary phases (CSPs)
or chiral selectors for gas chromatography (GC), liquid chromatography (LC) and
capillary electrophoresis (CE) rapidly opened a new dimension in the area of
separation technologies.
The business of developing single isomer drugs came about, because the chemical
production methods used for pharmaceuticals often produced racemic mixtures of
two enantiomers. In the case of thalidomide, it was shown that one enantiomer
was responsible for efficacy and another for side effects. Worldwide, the market
for chiral fine chemicals sold as single enantiomers was $6.63 billion in 2000
and is expected to grow at a rate of 13.2% annually, reaching $16.0 billion in
2007. The drug industry is the driving engine for this strong growth, accounting
for 81.2% of the total, equal to an overall worth of $5.38 billion, in the year
2000. The remaining $1.25 billion is divided among such uses as agricultural
chemicals. electronic chemicals, flavors and fragrances. The numbers look even
more impressive when considered as the sale of single-enantiomer compounds made
into the pharmaceutical formulations that people actually consume. The worldwide
market for dosage forms of single-enantiomer drugs was $123 billion in 2000,
increasing by 7.2%, from $115 billion in 1999. Geographically, the U.S. is the
biggest consumer of enantiomeric fine chemicals, contributing to a total North
American share of $3.98 billion, making up 60% of the total. European and Asian
consumption of enantiomeric fine chemicals is not expected to grow as fast, with
the North American share rising to 66.9% of the market in 2007, equivalent to
$10.7 billion. Some drug companies have patented and developed a racemic drug,
with the intention of patenting and developing a single enantiomer later. When
the patent on the racemate expires, the company can undercut generic competition
by launching the single-enantiomer. AstraZeneca, for instance, has developed
esomeprazole (Nexium), a single enantiomer version of its $6 billion anti-ulcer
drug omeprazole (Prilosec), which came off patent in 2002.
The drug industry will continue to have a strong growth in chiral compounds,
because of the efforts to improve drug efficacy and to cut development costs in
the face of regulatory pressures. Medicinal chemists are increasingly targeting
enzymes, hormones, and other compounds within patients? cells, as well as the
cells of microorganisms. Additional targets are receptors on cell surfaces.
These compounds and receptors are made up of chiral amino acids, carbohydrates,
and lipids. Drugs that are intended to interact with them must be enantiomeric,
in order to increase the chance of success.
In Iran, little attention has been paid to the importance of chiral drugs, both
in the regulatory sector and in the private sector, while production of
single-enantiomers especially by separation methods, is a profitable business.
The API manufacturers may produce or import cheaper crude racemic mixtures of
chiral drugs, and separate the active enantiomer and release it to the market. A
drug molecule such as esomeprazole seems to be an ideal candidate for this
business.
Dr Alireza Shafaati, Associate Professor, Pharmaceutical Chemistry Department,
School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran,
Iran. He can be reached at ashafaati@yahoo.com