INTRODUCTION
Chirality is an important geometric characteristic of the objects within
biological systems including amino acids, carbohydrates, and lipids as
well as drugs . In the latter, chirality might be associated with safety
issues through pharmacokinetic or pharmacodynamic variations, drug
interactions, or direct toxicological responses . Chiral drugs consist
of racemic mixtures, non-racemic mixtures, or pure enantiomers . Unlike
achiral drugs with no chiral center, this stereoisomeric chemistry
allows the opportunity to manipulate their composition or molecular
chirality to enhance efficacy and/or overcome tolerability problems . A
typical example of improving clinical efficacy could be given as
selective H1-receptor antagonist, cetirizine, whose R-enantiomer
levocetirizine has 30-fold higher binding affinity and lower renal
clearance compared to its parent racemic mixture . On the other hand,
thalidomide represents a well-known dramatic example of drug-induced
toxicity, with R-enantiomer responsible for the intended sedative effect
and S-enantiomer for the tragic phocomelia .
Use of pure enantiomers offers advantages including dose reduction,
simplification of dose-response relationship, diminution of
interindividual variability and toxicity from inactive enantiomers . In
fact, regulatory drug authorities encourage such chemical designations
for novel drug development . In addition, some racemic mixtures were
undergone chiral switch, where their pure enantiomers were launched with
same/similar indication . These have led to increased share of pure
enantiomers worldwide though still many racemic and non-racemic mixtures
are present . While several clinical efficacy and/or safety benefits
have been attributed to pure enantiomer drugs, there has been no
systematic analysis that investigated these aspects with respect to
chirality. In this study, we aimed to examine chiral status of the drugs
withdrawn from the market.