Some pharmaceutical industries have begun to market optically active pure
enantiomers of some drugs (Szelenyi et al. 1998; Nunez et al. 2009; LaPlante
et al. 2011; Mohan et al. 2017; Alkadi and Jbeily 2018; Calcaterra and D’Acquarica
2018). Most important chiral drugs include cardiovascular, analgesics, antiinflammatory, anticancer, antiviral and other applications. These are used for treating
respiratory diseases, the central nervous system, ophthalmic dermatology and gastrointestinal. The discussion on racemic drugs versus enantiomers caused a different
market policy, the so-called racemic switch. A “racemic switch” stands for the
application of only one enantiomer of a chiral drug, which was first approved as a
racemate. It can be inferred from the literature that around 856 billion US$ was the
intake price of the drugs in 2012 across the entire world (Lindsey 2013). It was also
assessed that around 30% input was represented by a single enantiomer. It is very
exciting to observe that 21% sale of enantiomeric pure drugs in 1996 had augmented
up to almost 50% in 2013 in the United States, and this percentage is constantly
growing owing to the growing population and the demographic development (Burke
and Henderson 2002; Mullard 2015).
At present, the economic influence of the industrial manufacturing of chiral drugs
is vast, and more than 50% of 500 top-selling drugs are single enantiomers. The sales
have sustained to grow extremely, and global yearly sales of enantiomeric drugs
surpassed 100 billion US$ for the first time in the year 2000, chiral drugs
representing nearly one third of all sales globally. Although some chiral switches
may be of fewer obvious benefit, or certainly harmful in some cases, inspiration by
the controlling agencies and the capability to understand the life cycle of a drug
promotes the trend. The research for novel chemical entities that can interrelate
precisely with distinct enzyme families may possibly lead to new therapies for
difficult illness processes (Reddy et al. 2000; Burke and Henderson 2002; Battiti
et al. 2019).
10.7 Challenges to Risk Assessment
Until today, there are less data accessible on enantioselective effects than on the
enantioselective fate of chiral pollutants, in spite of the fact that toxicity dissimilarities between enantiomers have been proved to vary up to more than 30 times. This
comparative deficiency of effect data is possibly the main obstruction to more
complete risk evaluations of chiral compounds. The enantiomers of a chiral molecule
may cause diverse biological effects due to the different enantioselective nature of
biological receptors. Nevertheless, the dissimilarity in effects produced by enantiomers may be more than just a quest of magnitude. Enantiomers may have totally
different modes of action (MOAs) and effects. Furthermore, interactions between
enantiomers of a drug have been revealed to yield unpredicted pharmacokinetic
profiles and pharmacodynamics characteristics (Mehvar and Brocks 2001). Correspondingly, it was shown that sometimes superior harmful effects, including carcinogenicity, are possible for a racemate than for either of the individual enantiomers
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10 Chirality in Environmental Toxicity and Fate Assessments
enantiomers of some drugs (Szelenyi et al. 1998; Nunez et al. 2009; LaPlante
et al. 2011; Mohan et al. 2017; Alkadi and Jbeily 2018; Calcaterra and D’Acquarica
2018). Most important chiral drugs include cardiovascular, analgesics, antiinflammatory, anticancer, antiviral and other applications. These are used for treating
respiratory diseases, the central nervous system, ophthalmic dermatology and gastrointestinal. The discussion on racemic drugs versus enantiomers caused a different
market policy, the so-called racemic switch. A “racemic switch” stands for the
application of only one enantiomer of a chiral drug, which was first approved as a
racemate. It can be inferred from the literature that around 856 billion US$ was the
intake price of the drugs in 2012 across the entire world (Lindsey 2013). It was also
assessed that around 30% input was represented by a single enantiomer. It is very
exciting to observe that 21% sale of enantiomeric pure drugs in 1996 had augmented
up to almost 50% in 2013 in the United States, and this percentage is constantly
growing owing to the growing population and the demographic development (Burke
and Henderson 2002; Mullard 2015).
At present, the economic influence of the industrial manufacturing of chiral drugs
is vast, and more than 50% of 500 top-selling drugs are single enantiomers. The sales
have sustained to grow extremely, and global yearly sales of enantiomeric drugs
surpassed 100 billion US$ for the first time in the year 2000, chiral drugs
representing nearly one third of all sales globally. Although some chiral switches
may be of fewer obvious benefit, or certainly harmful in some cases, inspiration by
the controlling agencies and the capability to understand the life cycle of a drug
promotes the trend. The research for novel chemical entities that can interrelate
precisely with distinct enzyme families may possibly lead to new therapies for
difficult illness processes (Reddy et al. 2000; Burke and Henderson 2002; Battiti
et al. 2019).
10.7 Challenges to Risk Assessment
Until today, there are less data accessible on enantioselective effects than on the
enantioselective fate of chiral pollutants, in spite of the fact that toxicity dissimilarities between enantiomers have been proved to vary up to more than 30 times. This
comparative deficiency of effect data is possibly the main obstruction to more
complete risk evaluations of chiral compounds. The enantiomers of a chiral molecule
may cause diverse biological effects due to the different enantioselective nature of
biological receptors. Nevertheless, the dissimilarity in effects produced by enantiomers may be more than just a quest of magnitude. Enantiomers may have totally
different modes of action (MOAs) and effects. Furthermore, interactions between
enantiomers of a drug have been revealed to yield unpredicted pharmacokinetic
profiles and pharmacodynamics characteristics (Mehvar and Brocks 2001). Correspondingly, it was shown that sometimes superior harmful effects, including carcinogenicity, are possible for a racemate than for either of the individual enantiomers
292
10 Chirality in Environmental Toxicity and Fate Assessments